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Cerebral creatine deficiency syndromes — theoretical families Each paper is placed by what it is for: why the brain needs creatine, how creatine is made and moved, how it is seen, what the disorders are, how patients are found, why its loss harms, or how it is restored. dot size = times cited 0 30 100 300 1,000+ hollow = no count (9) Energetics: creatine as the brain's energy buffer Creatine and phosphocreatine, through creatine kinase, buffer and carry high-energy phosphate, and roles beyond energy (neuromodulation, osmolyte) explain… Synthesis and transport: how creatine is made and moved Creatine is made by AGAT and GAMT and carried into cells by the SLC6A8 transporter; brain supply depends on limited blood-brain-barrier transport plus… Seeing creatine: in vivo MR spectroscopy In vivo NMR spectroscopy, first phosphorus and then localized proton MRS and spectroscopic imaging, made brain creatine measurable; its absence on MRS revealed the disorders and remains their defining… Defining the disorders: discovery, phenotype and genetics CTD, GAMT and AGAT deficiency were each discovered, delineated clinically and genetically, and followed over time, establishing who is affected, how, and… Finding patients: biochemical diagnosis and screening Guanidinoacetate, creatine and creatinine measurement in body fluids, functional assays and screening of high-risk and newborn populations turn a rare, treatable… Mechanisms of harm: models and pathophysiology Knockout animals, cell models and studies of guanidinoacetate toxicity show how creatine loss and precursor accumulation alter brain energetics, development… Restoring creatine: treatment Treatment runs from oral creatine that rescued the synthesis defects, through precursor and diet manipulation and presymptomatic therapy, to the still-unsolved search for a therapy that… 1880 1905 1930 1950 1965 1980 1985 1990 1995 2000 2002 2005 2007 2010 2012 2015 2017 2020 2022 2023 2024 2025 2026 Veech, R. L., Lawson, J. W., Cornell, N. W., & Krebs, H. A. (1979). Cytosolic phosphorylation potential. Journal of Biological Chemistry, 254(14), 6538-6547. Bessman, S. P., & Geiger, P. J. (1981). Transport of energy in muscle: The phosphorylcreatine shuttle. Science, 211(4481), 448-452. Bessman, S. P., & Carpenter, C. L. (1985). The creatine-creatine phosphate energy shuttle. Annual Review of Biochemistry, 54(1), 831-862. Erecińska, M., & Silver, I. A. (1989). ATP and brain function. Journal of Cerebral Blood Flow & Metabolism, 9(1), 2-19. Wallimann, T., Tokarska-Schlattner, M., & Schlattner, U. (2011). The creatine kinase system and pleiotropic effects of creatine. Amino Acids, 40(5), 1271-1296. Ackerman, J. J. H., Grove, T. H., Wong, G. G., Gadian, D. G., & Radda, G. K. (1980). Mapping of metabolites in whole animals by 31P NMR using surface coils. Nature, 283(5743), 167-170. Brown, T. R., Kincaid, B. M., & Ugurbil, K. (1982). NMR chemical shift imaging in three dimensions. Proceedings of the National Academy of Sciences, 79(11), 3523-3526. Haase, A., Frahm, J., Hanicke, W., & Matthaei, D. (1985). 1H NMR chemical shift selective (CHESS) imaging. Physics in Medicine and Biology, 30(4), 341-344. Ordidge, R. J., Connelly, A., & Lohman, J. A. B. (1986). Image-selected in vivo spectroscopy (ISIS). A new technique for spatially selective nmr spectroscopy. Journal of Magnetic Resonance, 66(2), 283-294. Frahm, J., Merboldt, K.-D., & Hänicke, W. (1987). Localized proton spectroscopy using stimulated echoes. Journal of Magnetic Resonance, 72(3), 502-508. Bottomley, P. A. (1987). Spatial localization in NMR spectroscopy in vivo. Annals of the New York Academy of Sciences, 508(1), 333-348. Frahm, J., Bruhn, H., Gyngell, M. L., Merboldt, K. D., Hänicke, W., & Sauter, R. (1989). Localized high-resolution proton NMR spectroscopy using stimulated echoes: Initial applications to human brain in vivo. Magnetic Resonance in Medicine, 9(1), 79-93. Miller, B. L. (1991). A review of chemical issues in 1H NMR spectroscopy: N-acetyl-l-aspartate, creatine and choline. NMR in Biomedicine, 4(2), 47-52. Gruetter, R. (1993). Automatic, localized in vivo adjustment of all first-and second-order shim coils. Magnetic Resonance in Medicine, 29(6), 804-811. Urenjak, J., Williams, S., Gadian, D., & Noble, M. (1993). Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. The Journal of Neuroscience, 13(3), 981-989. Brand, A., Richter-Landsberg, C., & Leibfritz, D. (1994). Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Developmental Neuroscience. Tkáč, I., Starčuk, Z., Choi, I. Y., & Gruetter, R. (1999). In vivo1H NMR spectroscopy of rat brain at 1 ms echo time. Magnetic Resonance in Medicine, 41(4), 649-656. Howarth, C., Gleeson, P., & Attwell, D. (2012). Updated energy budgets for neural computation in the neocortex and cerebellum. Journal of Cerebral Blood Flow & Metabolism, 32(7), 1222-1232. Kreis, R., Ernst, T., & Ross, B. D. (1993). Development of the human brain: In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magnetic Resonance in Medicine, 30(4), 424-437. Ames, A. (2000). CNS energy metabolism as related to function. Brain Research Reviews, 34(1-2), 42-68. Schlattner, U., Tokarska-Schlattner, M., & Wallimann, T. (2006). Mitochondrial creatine kinase in human health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1762(2), 164-180. Michaelis, T., Merboldt, K. D., Bruhn, H., Hänicke, W., & Frahm, J. (1993). Absolute concentrations of metabolites in the adult human brain in vivo: Quantification of localized proton MR spectra. Radiology, 187(1), 219-227. Hoult, D. I., Busby, S. J. W., Gadian, D. G., Radda, G. K., Richards, R. E., & Seeley, P. J. (1974). Observation of tissue metabolites using 31P nuclear magnetic resonance. Nature, 252(5481), 285-287. Lawson, J. W., & Veech, R. L. (1979). Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. Journal of Biological Chemistry, 254(14), 6528-6537. Frahm, J., Bruhn, H., Gyngell, M. L., Merboldt, K. D., Hänicke, W., & Sauter, R. (1989). Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites. Magnetic Resonance in Medicine, 11(1), 47-63. Ernst, T., Kreis, R., & Ross, B. D. (1993). Absolute quantitation of water and metabolites in the human brain. I. Compartments and Water. Journal of Magnetic Resonance, Series B, 102(1), 1-8. Petroff, O. A. C., Prichard, J. W., Behar, K. L., Alger, J. R., den Hollander, J. A., & Shulman, R. G. (1985). Cerebral intracellular pH by 31 P nuclear magnetic resonance spectroscopy. Neurology, 35(6), 781-781. Maudsley, A. A., Hilal, S. K., Perman, W. H., & Simon, H. E. (1983). Spatially resolved high resolution spectroscopy by “four-dimensional” NMR. Journal of Magnetic Resonance, 51(1), 147-152. Kreis, R., Ernst, T., & Ross, B. D. (1993). Absolute quantitation of water and metabolites in the human brain. II. Metabolite Concentrations. Journal of Magnetic Resonance, Series B, 102(1), 9-19. Meyer, R. A. (1988). A linear model of muscle respiration explains monoexponential phosphocreatine changes. American Journal of Physiology-Cell Physiology, 254(4), C548-C553. Meyer, R. A., Sweeney, H. L., & Kushmerick, M. J. (1984). A simple analysis of the "phosphocreatine shuttle". American Journal of Physiology-Cell Physiology, 246(5), C365-C377. Ellington, W. R. (2001). Evolution and physiological roles of phosphagen systems. Annual Review of Physiology, 63(1), 289-325. Pfeuffer, J., Tkáč, I., Provencher, S. W., & Gruetter, R. (1999). Toward an in vivo neurochemical profile: Quantification of 18 metabolites in short-echo-time 1H NMR spectra of the rat brain. Journal of Magnetic Resonance, 141(1), 104-120. Pouwels, P. J. W., & Frahm, J. (1998). Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magnetic Resonance in Medicine, 39(1), 53-60. Dzeja, P. P., & Terzic, A. (2003). Phosphotransfer networks and cellular energetics. Journal of Experimental Biology, 206(12), 2039-2047. Jacobus, W. E., & Lehninger, A. L. (1973). Creatine kinase of rat heart mitochondria. Journal of Biological Chemistry, 248(13), 4803-4810. Wyss, M., Smeitink, J., Wevers, R. A., & Wallimann, T. (1992). Mitochondrial creatine kinase: A key enzyme of aerobic energy metabolism. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1102(2), 119-166. Lawler, J. M., Barnes, W. S., Wu, G., Song, W., & Demaree, S. (2002). Direct antioxidant properties of creatine. Biochemical and Biophysical Research Communications, 290(1), 47-52. Jansen, J. F. A., Backes, W. H., Nicolay, K., & Kooi, M. E. (2006). 1H MR spectroscopy of the brain: Absolute quantification of metabolites. Radiology, 240(2), 318-332. Alle, H., Roth, A., & Geiger, J. R. P. (2009). Energy-efficient action potentials in hippocampal mossy fibers. Science, 325(5946), 1405-1408. Kuby, S. A., Noda, L., & Lardy, H. A. (1954). Adenosinetriphosphate-creatine transphosphorylase. Journal of Biological Chemistry, 209(1), 191-201. Fiske, C. H., & Subbarow, Y. (1929). Phosphocreatine. Journal of Biological Chemistry, 81(3), 629-679. Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T., & Widmer, H. R. (2008). Functions and effects of creatine in the central nervous system. Brain Research Bulletin, 76(4), 329-343. Duyn, J. H., Gillen, J., Sobering, G., van Zijl, P. C., & Moonen, C. T. (1993). Multisection proton MR spectroscopic imaging of the brain. Radiology, 188(1), 277-282. Wallimann, T., & Hemmer, W. (1994). Creatine kinase in non-muscle tissues and cells. Molecular and Cellular Biochemistry, 133-134(1), 193-220. Eppenberger, H. M., Dawson, D. M., & Kaplan, N. O. (1967). The comparative enzymology of creatine kinases. Journal of Biological Chemistry, 242(2), 204-209. Burt, C. T., Glonek, T., & Bárány, M. (1976). Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance. Journal of Biological Chemistry, 251(9), 2584-2591. Jacobs, H., Heldt, H. W., & Klingenberg, M. (1964). High activity of creatine kinase in mitochondria from muscle and brain and evidence for a separate mitochondrial isoenzyme of creatine kinase. Biochemical and Biophysical Research Communications, 16(6), 516-521. Pouwels, P. J. W., Brockmann, K., Kruse, B., Wilken, B., Wick, M., Hanefeld, F., & Frahm, J. (1999). Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatric Research, 46(4), 474-474. Hope, P. (1984). Cerebral energy metabolism studied with phosphorus nmr spectroscopy in normal and birth-asphyxiated infants. The Lancet, 324(8399), 366-370. van der Knaap, M. S., van der Grond, J., van Rijen, P. C., Faber, J. A., Valk, J., & Willemse, K. (1990). Age-dependent changes in localized proton and phosphorus MR spectroscopy of the brain. Radiology, 176(2), 509-515. Barker, P. B., Soher, B. J., Blackband, S. J., Chatham, J. C., Mathews, V. P., & Bryan, R. N. (1993). Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference. NMR in Biomedicine, 6(1), 89-94. Cady, E. B., Dawson, M. J., Hope, P. L., Tofts, P. S., Costello, A. M. de L., Delpy, D. T., Reynolds, E. O. R., & Wilkie, D. R. (1983). Non-invasive investigation of cerebral metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy. The Lancet, 321(8333), 1059-1062. Posse, S., Tedeschi, G., Risinger, R., Ogg, R., & Bihan, D. L. (1995). High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding. Magnetic Resonance in Medicine, 33(1), 34-40. Saks, V. A., Rosenshtraukh, L. V., Smirnov, V. N., & Chazov, E. I. (1978). Role of creatine phosphokinase in cellular function and metabolism. Canadian Journal of Physiology and Pharmacology, 56(5), 691-706. Christiansen, P., Henriksen, O., Stubgaard, M., Gideon, P., & Larsson, H. B. W. (1993). In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. Magnetic Resonance Imaging, 11(1), 107-118. Behar, K. L., den Hollander, J. A., Stromski, M. E., Ogino, T., Shulman, R. G., Petroff, O. A., & Prichard, J. W. (1983). High-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo. Proceedings of the National Academy of Sciences, 80(16), 4945-4948. Brosnan, J. T., da Silva, R. P., & Brosnan, M. E. (2011). The metabolic burden of creatine synthesis. Amino Acids, 40(5), 1325-1331. Soher, B. J., van Zijl, P. C. M., Duyn, J. H., & Barker, P. B. (1996). Quantitative proton MR spectroscopic imaging of the human brain. Magnetic Resonance in Medicine, 35(3), 356-363. Bottomley, P. A. (1989). Human in vivo NMR spectroscopy in diagnostic medicine: Clinical tool or research probe? Radiology, 170(1), 1-15. Kreis, R., Hofmann, L., Kuhlmann, B., Boesch, C., Bossi, E., & Hüppi, P. S. (2002). Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy. Magnetic Resonance in Medicine, 48(6), 949-958. Radda, G. K. (1986). The use of NMR spectroscopy for the understanding of disease. Science, 233(4764), 640-645. Michelson, D. J., Shevell, M. I., Sherr, E. H., Moeschler, J. B., Gropman, A. L., & Ashwal, S. (2011). Evidence report: Genetic and metabolic testing on children with global developmental delay [RETIRED]: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology, 77(17), 1629-1635. Saks, V. A., Khuchua, Z. A., Vasilyeva, E. V., Belikova, O. Y., & Kuznetsov, A. V. (1994). Metabolic compartmentation and substrate channelling in muscle cells: Role of coupled creatine kinases in in vivo regulation of cellular respiration: A synthesis. Molecular and Cellular Biochemistry, 133-134(1), 155-192. Eggleton, P., Elsden, S. R., & Gough, N. (1943). The estimation of creatine and of diacetyl. Biochemical Journal, 37(5), 526-529. Schulze, A. (2013). Creatine deficiency syndromes. In O. Dulac, M. Lassonde, & H. B. Sarnat (Eds.), Handbook of clinical neurology: Vol. 113. Pediatric neurology part III (pp. 1837-1843). Elsevier. Wallimann, T., Dolder, M., Schlattner, U., Eder, M., Hornemann, T., O'Gorman, E., Rück, A., & Brdiczka, D. (1998). Some new aspects of creatine kinase (CK): Compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology. BioFactors, 8(3-4), 229-234. Van Pilsum, J. F., Martin, R. P., Kito, E., & Hess, J. (1956). Determination of creatine, creatinine, arginine, guanidinoacetic acid, guanidine, and methyl-guanidine in biological fluids. Journal of Biological Chemistry, 222(1), 225-236. Joncquel-Chevalier Curt, M., Voicu, P.-M., Fontaine, M., Dessein, A.-F., Porchet, N., Mention-Mulliez, K., Dobbelaere, D., Soto-Ares, G., Cheillan, D., & Vamecq, J. (2015). Creatine biosynthesis and transport in health and disease. Biochimie, 119, 146-165. Moonen, C. T. W., Kienlin, M. V., Van Zijl, P. C. M., Cohen, J., Gillen, J., Daly, P., & Wolf, G. (1989). Comparison of single-shot localization methods (steam and press) for in vivo proton NMR spectroscopy. NMR in Biomedicine, 2(5-6), 201-208. Sestili, P., Martinelli, C., Bravi, G., Piccoli, G., Curci, R., Battistelli, M., Falcieri, E., Agostini, D., Gioacchini, A. M., & Stocchi, V. (2006). Creatine supplementation affords cytoprotection in oxidatively injured cultured mammalian cells via direct antioxidant activity. Free Radical Biology and Medicine, 40(5), 837-849. Fiske, C. H., & Subbarow, Y. (1927). The nature of the "inorganic phosphate" in voluntary muscle. Science, 65(1686), 401-403. van Karnebeek, C. D. M., & Stockler, S. (2012). Treatable inborn errors of metabolism causing intellectual disability: A systematic literature review. Molecular Genetics and Metabolism, 105(3), 368-381. Li, B. S. Y., Wang, H., & Gonen, O. (2003). Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy. Magnetic Resonance Imaging, 21(8), 923-928. Snow, R. J., & Murphy, R. M. (2001). Creatine and the creatine transporter: A review. Molecular and Cellular Biochemistry, 224(1-2), 169-181. Sestili, P., Martinelli, C., Colombo, E., Barbieri, E., Potenza, L., Sartini, S., & Fimognari, C. (2011). Creatine as an antioxidant. Amino Acids, 40(5), 1385-1396. Dawson, D. M., Eppenberger, H. M., & Kaplan, N. O. (1965). Creatine kinase: Evidence for a dimeric structure. Biochemical and Biophysical Research Communications, 21(4), 346-353. Béard, E., & Braissant, O. (2010). Synthesis and transport of creatine in the CNS: Importance for cerebral functions. Journal of Neurochemistry, 115(2), 297-313. Haris, M., Nanga, R. P. R., Singh, A., Cai, K., Kogan, F., Hariharan, H., & Reddy, R. (2012). Exchange rates of creatine kinase metabolites: Feasibility of imaging creatine by chemical exchange saturation transfer MRI. NMR in Biomedicine, 25(11), 1305-1309. Hanstock, C. C., Rothman, D. L., Prichard, J. W., Jue, T., & Shulman, R. G. (1988). Spatially localized 1H NMR spectra of metabolites in the human brain. Proceedings of the National Academy of Sciences, 85(6), 1821-1825. Tachikawa, M., Fukaya, M., Terasaki, T., Ohtsuki, S., & Watanabe, M. (2004). Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine kinases uCK-Mi and CK-B suggest a novel neuron–glial relationship for brain energy homeostasis. European Journal of Neuroscience, 20(1), 144-160. Eggleton, P., & Eggleton, G. P. (1927). The inorganic phosphate and a labile form of organic phosphate in the gastrocnemius of the frog. Biochemical Journal, 21(1), 190-195. Stockler, S., Schutz, P. W., & Salomons, G. S. (2007). Cerebral creatine deficiency syndromes: Clinical aspects, treatment and pathophysiology. In G. S. Salomons & M. Wyss (Eds.), Creatine and creatine kinase in health and disease (Subcellular Biochemistry, Vol. 46, pp. 149-166). Springer. Prichard, J. W., Alger, J. R., Behar, K. L., Petroff, O. A., & Shulman, R. G. (1983). Cerebral metabolic studies in vivo by 31P NMR. Proceedings of the National Academy of Sciences, 80(9), 2748-2751. Loike, J. D., Zalutsky, D. L., Kaback, E., Miranda, A. F., & Silverstein, S. C. (1988). Extracellular creatine regulates creatine transport in rat and human muscle cells. Proceedings of the National Academy of Sciences, 85(3), 807-811. Hemmer, W., & Wallimann, T. (1994). Functional aspects of creatine kinase in brain. Developmental Neuroscience. Tofts, P. S., & Wray, S. (1988). A critical assessment of methods of measuring metabolite concentrations by NMR spectroscopy. NMR in Biomedicine, 1(1), 1-10. Jost, C. R., Van der Zee, C. E. E. M., in 't Zandt, H. J. A., Oerlemans, F., Verheij, M., Streijger, F., Fransen, J., Heerschap, A., Cools, A. R., & Wieringa, B. (2002). Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility. European Journal of Neuroscience, 15(10), 1692-1706. Bloch, K., & Schoenheimer, R. (1941). The biological precursors of creatine. Journal of Biological Chemistry, 138(1), 167-194. Hüppi, P. S., Posse, S., Lazeyras, F., Burri, R., Bossi, E., & Herschkowitz, N. (1991). Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing human brain. Pediatric Research, 30(6), 574-578. Ennor, A. H., & Morrison, J. F. (1958). Biochemistry of the phosphagens and related guanidines. Physiological Reviews, 38(4), 631-674. Borsook, H., & Dubnoff, J. W. (1947). The hydrolysis of phosphocreatine and the origin of urinary creatinine. Journal of Biological Chemistry, 168(2), 493-510. Braissant, O., Henry, H., Béard, E., & Uldry, J. (2011). Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids, 40(5), 1315-1324. Bottomley, P. A., Charles, H. C., Roemer, P. B., Flamig, D., Engeseth, H., Edelstein, W. A., & Mueller, O. M. (1988). Human in vivo phosphate metabolite imaging with 31P NMR. Magnetic Resonance in Medicine, 7(3), 319-336. Folin, O. (1904). Beitrag zur Chemie des Kreatinins und Kreatins im Harne. Hoppe-Seyler´s Zeitschrift für physiologische Chemie, 41(3), 223-242. Hennig, J., Pfister, H., Ernst, T., & Ott, D. (1992). Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy. NMR in Biomedicine, 5(4), 193-199. Choe, C.-U., Atzler, D., Wild, P. S., Carter, A. M., Böger, R. H., Ojeda, F., Simova, O., Stockebrand, M., Lackner, K., Nabuurs, C., Marescau, B., Streichert, T., Müller, C., Lüneburg, N., De Deyn, P. P., Benndorf, R. A., Baldus, S., Gerloff, C., Blankenberg, S., … Schwedhelm, E. (2013). Homoarginine levels are regulated by l -Arginine:Glycine amidinotransferase and affect stroke outcome: Results from human and murine studies. Circulation, 128(13), 1451-1461. Stromberger, C., Bodamer, O. A., & Stöckler-Ipsiroglu, S. (2003). Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. Journal of Inherited Metabolic Disease, 26(2-3), 299-308. McGilvery, R. W., & Murray, T. W. (1974). Calculated equilibria of phosphocreatine and adenosine phosphates during utilization of high energy phosphate by muscle. Journal of Biological Chemistry, 249(18), 5845-5850. Sora, I., Richman, J., Santoro, G., Wei, H. B., Wang, Y., Vanderah, T., Horvath, R., Nguyen, M., Waite, S., Roeske, W. R., & Yamamura, H. I. (1994). The cloning and expression of a human creatine transporter. Biochemical and Biophysical Research Communications, 204(1), 419-427. Fitch, C. D., Shields, R. P., Payne, W. F., & Dacus, J. M. (1968). Creatine metabolism in skeletal muscle: III. Specificity of the creatine entry process. Journal of Biological Chemistry, 243(8), 2024-2027. Marescau, B., Deshmukh, D. R., Kockx, M., Possemiers, I., Qureshi, I. A., Wiechert, P., & De Deyn, P. P. (1992). Guanidino compounds in serum, urine, liver, kidney, and brain of man and some ureotelic animals. Metabolism, 41(5), 526-532. Wallimann, T. (1994). Bioenergetics: Dissecting the role of creatine kinase. Current Biology, 4(1), 42-46. Crim, M. C., Calloway, D. H., & Margen, S. (1975). Creatine metabolism in men: Urinary creatine and creatinine excretions with creatine feeding. The Journal of Nutrition, 105(4), 428-438. Connett, R. J. (1988). Analysis of metabolic control: New insights using scaled creatine kinase model. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 254(6), R949-R959. Braissant, O., Henry, H., Villard, A.-M., Speer, O., Wallimann, T., & Bachmann, C. (2005). Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1. BMC Developmental Biology, 5(1). Rackayova, V., Cudalbu, C., Pouwels, P. J. W., & Braissant, O. (2017). Creatine in the central nervous system: From magnetic resonance spectroscopy to creatine deficiencies. Analytical Biochemistry, 529, 144-157. Humm, A., Fritsche, E., Steinbacher, S., & Huber, R. (1997). Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: A mitochondrial enzyme involved in creatine biosynthesis. The EMBO Journal, 16(12), 3373-3385. Borsook, H., & Dubnoff, J. W. (1941). The formation of glycocyamine in animal tissues. Journal of Biological Chemistry, 138(1), 389-403. Walker, J. B. (1960). Metabolic control of creatine biosynthesis: I. Effect of dietary creatine. Journal of Biological Chemistry, 235(8), 2357-2361. Ipsiroglu, O. S., Stromberger, C., Ilas, J., Höger, H., Mühl, A., & Stöckler-Ipsiroglu, S. (2001). Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sciences, 69(15), 1805-1815. Streijger, F., Oerlemans, F., Ellenbroek, B., Jost, C., Wieringa, B., & Vanderzee, C. (2005). Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behavioural Brain Research, 157(2), 219-234. Bloch, K., Schoenheimer, R., & Rittenberg, D. (1941). Rate of formation and disappearance of body creatine in normal animals. Journal of Biological Chemistry, 138(1), 155-166. Braissant, O., & Henry, H. (2008). AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: A review. Journal of Inherited Metabolic Disease, 31(2), 230-239. Ganesan, V., Johnson, A., Connelly, A., Eckhardt, S., & Surtees, R. A. H. (1997). Guanidinoacetate methyltransferase deficiency: New clinical features. Pediatric Neurology, 17(2), 155-157. Cantoni, G. L., & Vignos, P. J. (1954). Enzymatic mechanism of creatine synthesis. Journal of Biological Chemistry, 209(2), 647-659. Bottomley, P. A., Edelstein, W. A., Foster, T. H., & Adams, W. A. (1985). In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: A window to metabolism? Proceedings of the National Academy of Sciences, 82(7), 2148-2152. Hoberman, H. D., Sims, E. A. H., & Peters, J. H. (1948). Creatine and creatinine metabolism in the normal male adult studied with the aid of isotopic nitrogen. Journal of Biological Chemistry, 172(1), 45-58. Kogan, F., Haris, M., Debrosse, C., Singh, A., Nanga, R. P., Cai, K., Hariharan, H., & Reddy, R. (2014). In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T: Muscle CrCEST at 3T. Journal of Magnetic Resonance Imaging, 40(3), 596-602. Hoytema van Konijnenburg, E. M. M., Wortmann, S. B., Koelewijn, M. J., Tseng, L. A., Houben, R., Stöckler-Ipsiroglu, S., Ferreira, C. R., & van Karnebeek, C. D. M. (2021). Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app. Orphanet Journal of Rare Diseases, 16(1). Chen, L., Barker, P. B., Weiss, R. G., van Zijl, P. C. M., & Xu, J. (2019). Creatine and phosphocreatine mapping of mouse skeletal muscle by a polynomial and Lorentzian line-shape fitting CEST method. Magnetic Resonance in Medicine, 81(1), 69-78. Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., & Schwartz, C. E. (2002). X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28. The American Journal of Human Genetics, 70(5), 1349-1356. Stöckler, S., Marescau, B., De Deyn, P. R., Trijbels, J. M. F., & Hanefeld, F. (1997). Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism, 46(10), 1189-1193. Schloss, P., Mayser, W., & Betz, H. (1994). The putative rat choline transporter CHOT1 transports creatine and is highly expressed in neural and muscle-rich tissues. Biochemical and Biophysical Research Communications, 198(2), 637-645. Braissant, O. (2012). Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. Journal of Inherited Metabolic Disease, 35(4), 655-664. Borsook, H., & Dubnoff, J. W. (1940). The formation of creatine from glycocyamine in the liver. Journal of Biological Chemistry, 132(2), 559-574. Luyten, P. R., & den Hollander, J. A. (1986). Observation of metabolites in the human brain by MR spectroscopy. Radiology, 161(3), 795-798. Leuzzi, V., Bianchi, M. C., Tosetti, M., Carducci, C., Cerquiglini, A., Cioni, G., & Antonozzi, I. (2000). Brain creatine depletion: Guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). Neurology, 55(9), 1407-1410. Van Pilsum, J. F., Stephens, G. C., & Taylor, D. (1972). Distribution of creatine, guanidinoacetate and the enzymes for their biosynthesis in the animal kingdom. Implications for phylogeny. Biochemical Journal, 126(2), 325-345. Battini, R., Leuzzi, V., Carducci, C., Tosetti, M., Bianchi, M. C., Item, C. B., Stöckler-Ipsiroglu, S., & Cioni, G. (2002). Creatine depletion in a new case with AGAT deficiency: Clinical and genetic study in a large pedigree. Molecular Genetics and Metabolism, 77(4), 326-331. Fitch, C. D., & Shields, R. P. (1966). Creatine metabolism in skeletal muscle: I. Creatine movement across muscle membranes. Journal of Biological Chemistry, 241(15), 3611-3614. Mayser, W., Schloss, P., & Betz, H. (1992). Primary structure and functional expression of a choline transporter expressed in the rat nervous system. FEBS Letters, 305(1), 31-36. Guthmiller, P., Van Pilsum, J. F., Boen, J. R., & McGuire, D. M. (1994). Cloning and sequencing of rat kidney L-arginine:glycine amidinotransferase. Studies on the mechanism of regulation by growth hormone and creatine. Journal of Biological Chemistry, 269(26), 17556-17560. deGrauw, T. J., Salomons, G. S., Cecil, K. M., Chuck, G., Newmeyer, A., Schapiro, M. B., & Jakobs, C. (2002). Congenital creatine transporter deficiency. Neuropediatrics, 33(5), 232-238. Whittingham, T. S., & Lipton, P. (1981). Cerebral synaptic transmission during anoxia is protected by creatine. Journal of Neurochemistry, 37(6), 1618-1621. Rae, C. D., & Bröer, S. (2015). Creatine as a booster for human brain function. How might it work? Neurochemistry International, 89, 249-259. Wyss, M., & Wallimann, T. (1994). Creatine metabolism and the consequences of creatine depletion in muscle. Molecular and Cellular Biochemistry, 133-134(1), 51-66. Nasrallah, F., Feki, M., & Kaabachi, N. (2010). Creatine and creatine deficiency syndromes: Biochemical and clinical aspects. Pediatric Neurology, 42(3), 163-171. Lygate, C. A., Aksentijevic, D., Dawson, D., ten Hove, M., Phillips, D., de Bono, J. P., Medway, D. J., Sebag-Montefiore, L., Hunyor, I., Channon, K. M., Clarke, K., Zervou, S., Watkins, H., Balaban, R. S., & Neubauer, S. (2013). Living without creatine: Unchanged exercise capacity and response to chronic myocardial infarction in creatine-deficient mice. Circulation Research, 112(6), 945-955. Chen, L., Zeng, H., Xu, X., Yadav, N. N., Cai, S., Puts, N. A., Barker, P. B., Li, T., Weiss, R. G., van Zijl, P. C. M., & Xu, J. (2017). Investigation of the contribution of total creatine to the CEST Z-spectrum of brain using a knockout mouse model. NMR in Biomedicine, 30(12). McGuire, D. M., Gross, M. D., Van Pilsum, J. F., & Towle, H. C. (1984). Repression of rat kidney L-arginine:glycine amidinotransferase synthesis by creatine at a pretranslational level. Journal of Biological Chemistry, 259(19), 12034-12038. Bodamer, O. A., Bloesch, S. M., Gregg, A. R., Stockler-Ipsiroglu, S., & O'Brien, W. E. (2001). Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry. Clinica Chimica Acta, 308(1-2), 173-178. Longo, N., Ardon, O., Vanzo, R., Schwartz, E., & Pasquali, M. (2011). Disorders of creatine transport and metabolism. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 157(1), 72-78. Peral, M. J., García-Delgado, M., Calonge, M. L., Durán, J. M., De La Horra, M. C., Wallimann, T., Speer, O., & Ilundáin, A. A. (2002). Human, rat and chicken small intestinal Na+-Cl−-creatine transporter: Functional, molecular characterization and localization. The Journal of Physiology, 545(1), 133-144. Kaldis, P., Hemmer, W., Zanolla, E., Holtzman, D., & Wallimann, T. (1996). 'Hot spots' of creatine kinase localization in brain: Cerebellum, hippocampus and choroid plexus. Developmental Neuroscience, 18(5-6), 542-554. Bizzi, A., Bugiani, M., Salomons, G. S., Hunneman, D. H., Moroni, I., Estienne, M., Danesi, U., Jakobs, C., & Uziel, G. (2002). X-linked creatine deficiency syndrome: A novel mutation in creatine transporter gene SLC6A8. Annals of Neurology, 52(2), 227-231. Crim, M. C., Calloway, D. H., & Margen, S. (1976). Creatine metabolism in men: Creatine pool size and turnover in relation to creatine intake. The Journal of Nutrition, 106(3), 371-381. Bottomley, P. A., Hart, H. R., Edelstein, W. A., Schenck, J. F., Smith, L. S., Leue, W. M., Mueller, O. M., & Redington, R. W. (1983). Nmr imaging/spectroscopy system to study both anatomy and metabolism. The Lancet, 322(8344), 273-274. van der Knaap, M. S., Verhoeven, N. M., Maaswinkel-Mooij, P., Pouwels, P. J. W., Onkenhout, W., Peeters, E. A. J., Stöckler-Ipsiroglu, S., & Jakobs, C. (2000). Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect. Annals of Neurology, 47(4), 540-543. Folin, O. (1914). On the determination of creatinine and creatine in blood, milk and tissues. Journal of Biological Chemistry, 17(4), 475-481. Choe, C.-U., Nabuurs, C., Stockebrand, M. C., Neu, A., Nunes, P., Morellini, F., Sauter, K., Schillemeit, S., Hermans-Borgmeyer, I., Marescau, B., Heerschap, A., & Isbrandt, D. (2013). L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome. Human Molecular Genetics, 22(1), 110-123. Nabuurs, C. I., Choe, C. U., Veltien, A., Kan, H. E., van Loon, L. J. C., Rodenburg, R. J. T., Matschke, J., Wieringa, B., Kemp, G. J., Isbrandt, D., & Heerschap, A. (2013). Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake. The Journal of Physiology, 591(2), 571-592. Dai, W., Vinnakota, S., Qian, X., Kunze, D. L., & Sarkar, H. K. (1999). Molecular characterization of the human CRT-1 creatine transporter expressed inXenopusOocytes. Archives of Biochemistry and Biophysics, 361(1), 75-84. Möller, A., & Hamprecht, B. (1989). Creatine transport in cultured cells of rat and mouse brain. Journal of Neurochemistry, 52(2), 544-550. Reichold, M., Klootwijk, E. D., Reinders, J., Otto, E. A., Milani, M., Broeker, C., Laing, C., Wiesner, J., Devi, S., Zhou, W., Schmitt, R., Tegtmeier, I., Sterner, C., Doellerer, H., Renner, K., Oefner, P. J., Dettmer, K., Simbuerger, J. M., Witzgall, R., … Kleta, R. (2018). Glycine amidinotransferase (GATM), renal Fanconi syndrome, and kidney failure. Journal of the American Society of Nephrology, 29(7), 1849-1858. Terheggen, H. G., Schwenk, A., Lowenthal, A., Van Sande, M., & Colombo, J. P. (1969). Argininæmia with arginase deficiency. The Lancet, 294(7623), 748-749. Manos, P., Bryan, G. K., & Edmond, J. (1991). Creatine kinase activity in postnatal rat brain development and in cultured neurons, astrocytes, and oligodendrocytes. Journal of Neurochemistry, 56(6), 2101-2107. van de Kamp, J., Mancini, G., Pouwels, P., Betsalel, O., van Dooren, S., de Koning, I., Steenweg, M., Jakobs, C., van der Knaap, M., & Salomons, G. (2011). Clinical features and X-inactivation in females heterozygous for creatine transporter defect. Clinical Genetics, 79(3), 264-272. Carter, A. J., Müller, R. E., Pschorn, U., & Stransky, W. (1995). Preincubation with creatine enhances levels of creatine phosphate and prevents anoxic damage in rat hippocampal slices. Journal of Neurochemistry, 64(6), 2691-2699. Eggleton, P., & Eggleton, G. P. (1927). The physiological significance of ‘phosphagen’. The Journal of Physiology, 63(2), 155-161. Sipilä, I. (1980). Inhibition of arginine-glycine amidinotransferase by ornithine. A possible mechanism for the muscular and chorioretinal atrophies in gyrate atrophy of the choroid and retina with hyperornithinemia. Biochimica et Biophysica Acta (BBA) - Enzymology, 613(1), 79-84. Dringen, R., Verleysdonk, S., Hamprecht, B., Willker, W., Leibfritz, D., & Brand, A. (1998). Metabolism of glycine in primary astroglial cells: Synthesis of creatine, serine, and glutathione. Journal of Neurochemistry, 70(2), 835-840. Christie, D. L. (2007). Functional insights into the creatine transporter. In G. S. Salomons & M. Wyss (Eds.), Creatine and creatine kinase in health and disease (Subcellular Biochemistry, Vol. 46, pp. 99-118). Springer. Jinnai, D., Sawai, A., & Mori, A. (1966). γ-Guanidinobutyric acid as a convulsive substance. Nature, 212(5062), 617-617. Póo-Argüelles, P., Arias, A., Vilaseca, M. A., Ribes, A., Artuch, R., Sans-Fito, A., Moreno, A., Jakobs, C., & Salomons, G. (2006). X-linked creatine transporter deficiency in two patients with severe mental retardation and autism. Journal of Inherited Metabolic Disease, 29(1), 220-223. Balestrino, M., Lensman, M., Parodi, M., Perasso, L., Rebaudo, R., Melani, R., Polenov, S., & Cupello, A. (2002). Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage. Amino Acids, 23(1-3), 221-229. Mercimek-Mahmutoglu, S., Connolly, M. B., Poskitt, K. J., Horvath, G. A., Lowry, N., Salomons, G. S., Casey, B., Sinclair, G., Davis, C., Jakobs, C., & Stockler-Ipsiroglu, S. (2010). Treatment of intractable epilepsy in a female with SLC6A8 deficiency. Molecular Genetics and Metabolism, 101(4), 409-412. Bothwell, J. H., Rae, C., Dixon, R. M., Styles, P., & Bhakoo, K. K. (2001). Hypo-osmotic swelling-activated release of organic osmolytes in brain slices: Implications for brain oedema in vivo. Journal of Neurochemistry, 77(6), 1632-1640. Wallimann, T., Wegmann, G., Moser, H., Huber, R., & Eppenberger, H. M. (1986). High content of creatine kinase in chicken retina: Compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells. Proceedings of the National Academy of Sciences, 83(11), 3816-3819. Walker, J. B. (1961). Metabolic control of creatine biosynthesis: II. Restoration of transamidinase activity following creatine repression. Journal of Biological Chemistry, 236(2), 493-498. Braissant, O., Bachmann, C., & Henry, H. (2007). Expression and function of AGAT, GAMT and CT1 in the mammalian brain. In G. S. Salomons & M. Wyss (Eds.), Creatine and creatine kinase in health and disease (Subcellular Biochemistry, Vol. 46, pp. 67-81). Springer. Alfieri, R. R., Bonelli, M. A., Cavazzoni, A., Brigotti, M., Fumarola, C., Sestili, P., Mozzoni, P., De Palma, G., Mutti, A., Carnicelli, D., Vacondio, F., Silva, C., Borghetti, A. F., Wheeler, K. P., & Petronini, P. G. (2006). Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. The Journal of Physiology, 576(2), 391-401. Saltarelli, M. D., Bauman, A. L., Moore, K. R., Bradley, C. C., & Blakely, R. D. (1996). Expression of the rat brain creatine transporter in situ and in transfected HeLa cells. Developmental Neuroscience, 18(5-6), 524-534. Arias, A., Corbella, M., Fons, C., Sempere, A., García-Villoria, J., Ormazabal, A., Poo, P., Pineda, M., Vilaseca, M. A., Campistol, J., Briones, P., Pàmpols, T., Salomons, G. S., Ribes, A., & Artuch, R. (2007). Creatine transporter deficiency: Prevalence among patients with mental retardation and pitfalls in metabolite screening. Clinical Biochemistry, 40(16-17), 1328-1331. Dunbar, M., Jaggumantri, S., Sargent, M., Stockler-Ipsiroglu, S., & van Karnebeek, C. D. M. (2014). Treatment of X-linked creatine transporter (SLC6A8) deficiency: Systematic review of the literature and three new cases. Molecular Genetics and Metabolism, 112(4), 259-274. Saks, V., Kaambre, T., Guzun, R., Anmann, T., Sikk, P., Schlattner, U., Wallimann, T., Aliev, M., & Vendelin, M. (2007). The creatine kinase phosphotransfer network: Thermodynamic and kinetic considerations, the impact of the mitochondrial outer membrane and modelling approaches. In G. S. Salomons & M. Wyss (Eds.), Creatine and creatine kinase in health and disease (Subcellular Biochemistry, Vol. 46, pp. 27-65). Springer. Perasso, L., Cupello, A., Lunardi, G. L., Principato, C., Gandolfo, C., & Balestrino, M. (2003). Kinetics of creatine in blood and brain after intraperitoneal injection in the rat. Brain Research, 974(1-2), 37-42. Ensenauer, R., Thiel, T., Schwab, K. O., Tacke, U., Stöckler-Ipsiroglu, S., Schulze, A., Hennig, J., & Lehnert, W. (2004). Guanidinoacetate methyltransferase deficiency: Differences of creatine uptake in human brain and muscle. Molecular Genetics and Metabolism, 82(3), 208-213. Fernandes-Pires, G., & Braissant, O. (2022). Current and potential new treatment strategies for creatine deficiency syndromes. Molecular Genetics and Metabolism, 135(1), 15-26. Sakaguchi, S. (1925). Über eine neue Farbenreaktion von Protein und Arginin. The Journal of Biochemistry, 5(1), 25-31. Dhar, S. U., Scaglia, F., Li, F. Y., Smith, L., Barshop, B. A., Eng, C. M., Haas, R. H., Hunter, J. V., Lotze, T., Maranda, B., Willis, M., Abdenur, J. E., Chen, E., O’Brien, W., & Wong, L.-J. C. (2009). Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Molecular Genetics and Metabolism, 96(1), 38-43. Hiraga, Y., & Kinoshita, T. (1981). Post-column derivatization of guanidino compounds in high-performance liquid chromatography using ninhydrin. Journal of Chromatography B: Biomedical Sciences and Applications, 226(1), 43-51. Schulze, A., & Battini, R. (2007). Pre-symptomatic treatment of creatine biosynthesis defects. In Creatine and Creatine Kinase in Health and Disease (pp. 167-181). Springer Netherlands. Iyer, G. S., Krahe, R., Goodwin, L. A., Doggett, N. A., Siciliano, M. J., Funanage, V. L., & Proujansky, R. (1996). Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28. Genomics, 34(1), 143-146. Anselm, I. M., Alkuraya, F. S., Salomons, G. S., Jakobs, C., Fulton, A. B., Mazumdar, M., Rivkin, M., Frye, R., Poussaint, T. Y., & Marsden, D. (2006). X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype. Journal of Inherited Metabolic Disease, 29(1), 214-219. Rosenberg, E. H., Martínez Muñoz, C., Betsalel, O. T., van Dooren, S. J. M., Fernandez, M., Jakobs, C., deGrauw, T. J., Kleefstra, T., Schwartz, C. E., & Salomons, G. S. (2007). Functional characterization of missense variants in the creatine transporter gene (SLC6A8): Improved diagnostic application. Human Mutation, 28(9), 890-896. Jacobus, W. E. (1985). Theoretical support for the heart phosphocreatine energy transport shuttle based on the intracellular diffusion limited mobility of ADP. Biochemical and Biophysical Research Communications, 133(3), 1035-1041. Daly, M. M., & Seifter, S. (1980). Uptake of creatine by cultured cells. Archives of Biochemistry and Biophysics, 203(1), 317-324. Leuzzi, V., Mastrangelo, M., Battini, R., & Cioni, G. (2013). Inborn errors of creatine metabolism and epilepsy. Epilepsia, 54(2), 217-227. Stockler-Ipsiroglu, S., & van Karnebeek, C. D. M. (2014). Cerebral creatine deficiencies: A group of treatable intellectual developmental disorders. Seminars in Neurology, 34(03), 350-356. Stockler-Ipsiroglu, S., Apatean, D., Battini, R., DeBrosse, S., Dessoffy, K., Edvardson, S., Eichler, F., Johnston, K., Koeller, D. M., Nouioua, S., Tazir, M., Verma, A., Dowling, M. D., Wierenga, K. J., Wierenga, A. M., Zhang, V., & Wong, L.-J. C. (2015). Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116(4), 252-259. Verhoeven, N. M., Salomons, G. S., & Jakobs, C. (2005). Laboratory diagnosis of defects of creatine biosynthesis and transport. Clinica Chimica Acta, 361(1-2), 1-9. Hiramatsu, M. (2003). A role for guanidino compounds in the brain. Molecular and Cellular Biochemistry, 244(1-2), 57-62. Valayannopoulos, V., Boddaert, N., Chabli, A., Barbier, V., Desguerre, I., Philippe, A., Afenjar, A., Mazzuca, M., Cheillan, D., Munnich, A., de Keyzer, Y., Jakobs, C., Salomons, G. S., & de Lonlay, P. (2012). Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect. Journal of Inherited Metabolic Disease, 35(1), 151-157. Sweeney, H. L. (1994). The importance of the creatine kinase reaction: The concept of metabolic capacitance. Medicine & Science in Sports & Exercise, 26(1), 30???36. Mori, A. (1987). Biochemistry and neurotoxicology of guanidino compounds: History and recent advances. The Pavlovian Journal of Biological Science, 22(3), 85-94. Koga, Y., Takahashi, H., Oikawa, D., Tachibana, T., Denbow, D. M., & Furuse, M. (2005). Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks. Neuroscience, 132(1), 65-71. Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., & Antonozzi, I. (2002). Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: An effective diagnostic tool for the biochemical diagnosis of Arginine:Glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clinical Chemistry, 48(10), 1772-1778. Ratner, S., & Rochovansky, O. (1956). Biosynthesis of guanidinoacetic acid. I. Purification and properties of transamidinase. Archives of Biochemistry and Biophysics, 63(2), 277-295. Newmeyer, A., Cecil, K. M., Schapiro, M., Clark, J. F., & Degrauw, T. J. (2005). Incidence of brain creatine transporter deficiency in males with developmental delay referred for brain magnetic resonance imaging. Journal of Developmental & Behavioral Pediatrics, 26(4), 276-282. Gregor, P., Nash, S. R., Caron, M. G., Seldin, M. F., & Warren, S. T. (1995). Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD. Genomics, 25(1), 332-333. Mak, C. S. W., Waldvogel, H. J., Dodd, J. R., Gilbert, R. T., Lowe, M. T. J., Birch, N. P., Faull, R. L. M., & Christie, D. L. (2009). Immunohistochemical localisation of the creatine transporter in the rat brain. Neuroscience, 163(2), 571-585. Ireland, Z., Russell, A. P., Wallimann, T., Walker, D. W., & Snow, R. (2009). Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC Developmental Biology, 9(1). García-Cazorla, A., Wolf, N. I., Serrano, M., Moog, U., Pérez-Dueñas, B., Póo, P., Pineda, M., Campistol, J., & Hoffmann, G. F. (2009). Mental retardation and inborn errors of metabolism. Journal of Inherited Metabolic Disease, 32(5), 597-608. Caldeira Araújo, H., Smit, W., Verhoeven, N. M., Salomons, G. S., Silva, S., Vasconcelos, R., Tomás, H., Almeida, I. T. D., Jakobs, C., & Duran, M. (2005). Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation. American Journal of Medical Genetics Part A, 133A(2), 122-127. Mancini, G. M. S., Catsman-Berrevoets, C. E., de Coo, I. F. M., Aarsen, F. K., Kamphoven, J. H. J., Huijmans, J. G., Duran, M., van der Knaap, M. S., Jakobs, C., & Salomons, G. S. (2005). Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families. American Journal of Medical Genetics Part A, 132A(3), 288-295. Carducci, C., Santagata, S., Leuzzi, V., Carducci, C., Artiola, C., Giovanniello, T., Battini, R., & Antonozzi, I. (2006). Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry. Clinica Chimica Acta, 364(1-2), 180-187. Hanna-El-Daher, L., & Braissant, O. (2016). Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models? Amino Acids, 48(8), 1877-1895. Renema, W. K. J., Schmidt, A., van Asten, J. J. A., Oerlemans, F., Ullrich, K., Wieringa, B., Isbrandt, D., & Heerschap, A. (2003). MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)-deficient mice: Validation of an animal model to study creatine deficiency. Magnetic Resonance in Medicine, 50(5), 936-943. Perna, M. K., Kokenge, A. N., Miles, K. N., Udobi, K. C., Clark, J. F., Pyne-Geithman, G. J., Khuchua, Z., & Skelton, M. R. (2016). Creatine transporter deficiency leads to increased whole body and cellular metabolism. Amino Acids, 48(8), 2057-2065. Boehm, E. A., Radda, G. K., Tomlin, H., & Clark, J. F. (1996). The utilisation of creatine and its analogues by cytosolic and mitochondrial creatine kinase. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1274(3), 119-128. in 't Zandt, H. J. A., Renema, W. K. J., Streijger, F., Jost, C., Klomp, D. W. J., Oerlemans, F., Van der Zee, C. E. E. M., Wieringa, B., & Heerschap, A. (2004). Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: A quantitative in vivo1H and 31P magnetic resonance study. Journal of Neurochemistry, 90(6), 1321-1330. Item, C. B., Mercimek-Mahmutoglu, S., Battini, R., Edlinger-Horvat, C., Stromberger, C., Bodamer, O., Mühl, A., Vilaseca, M. A., Korall, H., & Stöckler-Ipsiroglu, S. (2004). Characterization of seven novel mutations in seven patients with GAMT deficiency: Mutations in brief. Human Mutation, 23(5), 524-524. Clark, J. F., & Cecil, K. M. (2015). Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes. Pediatric Research, 77(3), 398-405. Braissant, O., Cagnon, L., Monnet-Tschudi, F., Speer, O., Wallimann, T., Honegger, P., & Henry, H. (2008). Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency. European Journal of Neuroscience, 27(7), 1673-1685. Fons, C., Sempere, A., Arias, A., López-Sala, A., Póo, P., Pineda, M., Mas, A., Vilaseca, M. A., Salomons, G. S., Ribes, A., Artuch, R., & Campistol, J. (2008). Arginine supplementation in four patients with X-linked creatine transporter defect. Journal of Inherited Metabolic Disease, 31(6), 724-728. McGuire, D. M., Gross, M. D., Elde, R. P., & van Pilsum, J. F. (1986). Localization of L-arginine-glycine amidinotransferase protein in rat tissues by immunofluorescence microscopy. Journal of Histochemistry & Cytochemistry, 34(4), 429-435. Tachikawa, M., Fujinawa, J., Takahashi, M., Kasai, Y., Fukaya, M., Sakai, K., Yamazaki, M., Tomi, M., Watanabe, M., Sakimura, K., Terasaki, T., & Hosoya, K. (2008). Expression and possible role of creatine transporter in the brain and at the blood-cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant. Journal of Neurochemistry, 107(3), 768-778. van de Kamp, J. M., Pouwels, P. J. W., Aarsen, F. K., ten Hoopen, L. W., Knol, D. L., de Klerk, J. B., de Coo, I. F., Huijmans, J. G. M., Jakobs, C., van der Knaap, M. S., Salomons, G. S., & Mancini, G. M. S. (2012). Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect. Journal of Inherited Metabolic Disease, 35(1), 141-149. Abplanalp, J., Laczko, E., Philp, N. J., Neidhardt, J., Zuercher, J., Braun, P., Schorderet, D. F., Munier, F. L., Verrey, F., Berger, W., Camargo, S. M. R., & Kloeckener-Gruissem, B. (2013). The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter. Human Molecular Genetics, 22(16), 3218-3226. van Karnebeek, C. D., & Stockler-Ipsiroglu, S. (2014). Early identification of treatable inborn errors of metabolism in children with intellectual disability: The treatable intellectual disability endeavor protocol in British Columbia. Paediatrics & Child Health, 19(9), 469-471. Lunardi, G., Parodi, A., Perasso, L., Pohvozcheva, A. V., Scarrone, S., Adriano, E., Florio, T., Gandolfo, C., Cupello, A., Burov, S. V., & Balestrino, M. (2006). The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds. Neuroscience, 142(4), 991-997. Chilosi, A., Leuzzi, V., Battini, R., Tosetti, M., Ferretti, G., Comparini, A., Casarano, M., Moretti, E., Alessandrì, M. G., Bianchi, M. C., & Cioni, G. (2008). Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. Neurocase, 14(2), 151-161. De Deyn, P. P., Marescau, B., & Macdonald, R. L. (1991). Guanidino compounds that are increased in hyperargininemia inhibit GABA and glycine responses on mouse neurons in cell culture. Epilepsy Research, 8(2), 134-141. Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M., & Katz-Brull, R. (2010). L-arginine:glycine amidinotransferase (AGAT) deficiency: Clinical presentation and response to treatment in two patients with a novel mutation. Molecular Genetics and Metabolism, 101(2-3), 228-232. Cognat, S., Cheillan, D., Piraud, M., Roos, B., Jakobs, C., & Vianey-Saban, C. (2004). Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography–tandem mass spectrometry. Clinical Chemistry, 50(8), 1459-1461. Chamberlain, K. A., Chapey, K. S., Nanescu, S. E., & Huang, J. K. (2017). Creatine enhances mitochondrial-mediated oligodendrocyte survival after demyelinating injury. The Journal of Neuroscience, 37(6), 1479-1492. Lowe, M. T. J., Faull, R. L. M., Christie, D. L., & Waldvogel, H. J. (2015). Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity. Journal of Comparative Neurology, 523(5), 699-725. Pisano, J. J., Mitoma, C., & Udenfriend, S. (1957). Biosynthesis of γ-guanidinobutyric acid from γ-aminobutyric acid and arginine. Nature, 180(4595), 1125-1126. Baroncelli, L., Alessandrì, M. G., Tola, J., Putignano, E., Migliore, M., Amendola, E., Gross, C., Leuzzi, V., Cioni, G., & Pizzorusso, T. (2014). A novel mouse model of creatine transporter deficiency. F1000Research, 3, 228. Stockebrand, M., Sasani, A., Das, D., Hornig, S., Hermans-Borgmeyer, I., Lake, H. A., Isbrandt, D., Lygate, C. A., Heerschap, A., Neu, A., & Choe, C.-U. (2018). A mouse model of creatine transporter deficiency reveals impaired motor function and muscle energy metabolism. Frontiers in Physiology, 9. Dodd, J. R., & Christie, D. L. (2001). Cysteine 144 in the third transmembrane domain of the creatine transporter is located close to a substrate-binding site. Journal of Biological Chemistry, 276(50), 46983-46988. Farr, C. V., El-Kasaby, A., Freissmuth, M., & Sucic, S. (2020). The creatine transporter unfolded: A knotty premise in the cerebral creatine deficiency syndrome. Frontiers in Synaptic Neuroscience, 12. Royes, L. F. F., Fighera, M. R., Furian, A. F., Oliveira, M. S., Fiorenza, N. G., Ferreira, J., da Silva, A. C., Priel, M. R., Ueda, É. S., Calixto, J. B., Cavalheiro, E. A., & Mello, C. F. (2008). Neuromodulatory effect of creatine on extracellular action potentials in rat hippocampus: Role of NMDA receptors. Neurochemistry International, 53(1-2), 33-37. Walker, J. B. (1959). Repression of arginine-glycine transamidinase activity by dietary creatine. Biochimica et Biophysica Acta, 36(2), 574-575. Defalco, A. J., & Davies, R. K. (1961). The synthesis of creatine by the brain of the intact rat*. Journal of Neurochemistry, 7(4), 308-312. Puusepp, H., Kall, K., Salomons, G. S., Talvik, I., Männamaa, M., Rein, R., Jakobs, C., & Õunap, K. (2010). The screening of SLC6A8 deficiency among Estonian families with X-linked mental retardation. Journal of Inherited Metabolic Disease, 33(S3), 5-11. Baroncelli, L., Molinaro, A., Cacciante, F., Alessandrì, M. G., Napoli, D., Putignano, E., Tola, J., Leuzzi, V., Cioni, G., & Pizzorusso, T. (2016). A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging. Human Molecular Genetics, 25(19), 4186-4200. El-Kasaby, A., Kasture, A., Koban, F., Hotka, M., Asjad, H. M. M., Kubista, H., Freissmuth, M., & Sucic, S. (2019). Rescue by 4-phenylbutyrate of several misfolded creatine transporter-1 variants linked to the creatine transporter deficiency syndrome. Neuropharmacology, 161, 107572. Hemmer, W., Zanolla, E., Furter-Graves, E. M., Eppenberger, H. M., & Wallimann, T. (1994). Creatine kinase isoenzymes in chicken cerebellum: Specific localization of brain-type creatine kinase in Bergmann glial cells and muscle-type creatine kinase in Purkinje neurons. European Journal of Neuroscience, 6(4), 538-549. Tachikawa, M., Kasai, Y., Yokoyama, R., Fujinawa, J., Ganapathy, V., Terasaki, T., & Hosoya, K. (2009). The blood–brain barrier transport and cerebral distribution of guanidinoacetate in rats: Involvement of creatine and taurine transporters. Journal of Neurochemistry, 111(2), 499-509. Mancardi, M. M., Caruso, U., Schiaffino, M. C., Baglietto, M. G., Rossi, A., Battaglia, F. M., Salomons, G. S., Jakobs, C., Zara, F., Veneselli, E., & Gaggero, R. (2007). Severe epilepsy in X-linked creatine transporter defect (CRTR-D). Epilepsia, 48(6), 1211-1213. Yamamoto, Y., Manji, T., Saito, A., Maeda, K., & Ohta, K. (1979). Ion-exchange chromatographic separation and fluorometric detection of guanidino compounds in physiologic fluids. Journal of Chromatography B: Biomedical Sciences and Applications, 162(3), 327-340. Mercimek-Mahmutoglu, S., Ndika, J., Kanhai, W., Billette de Villemeur, T., Cheillan, D., Christensen, E., Dorison, N., Hannig, V., Hendriks, Y., Hofstede, F. C., Lion-Francois, L., Lund, A. M., Mundy, H., Pitelet, G., Raspall-Chaure, M., Scott-Schwoerer, J. A., Szakszon, K., Valayannopoulos, V., Williams, M., & Salomons, G. S. (2014). Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Human Mutation, 35(4), 462-469. Ilas, J., Mühl, A., & Stöckler-Ipsiroglu, S. (2000). Guanidinoacetate methyltransferase (GAMT) deficiency: Non-invasive enzymatic diagnosis of a newly recognized inborn error of metabolism. Clinica Chimica Acta, 290(2), 179-188. Kan, H. E., Renema, W. K. J., Isbrandt, D., & Heerschap, A. (2004). Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase. The Journal of Physiology, 560(1), 219-229. Bruun, T. U. J., Sidky, S., Bandeira, A. O., Debray, F.-G., Ficicioglu, C., Goldstein, J., Joost, K., Koeberl, D. D., Luísa, D., Nassogne, M.-C., O’Sullivan, S., Õunap, K., Schulze, A., van Maldergem, L., Salomons, G. S., & Mercimek-Andrews, S. (2018). Treatment outcome of creatine transporter deficiency: International retrospective cohort study. Metabolic Brain Disease, 33(3), 875-884. Happe, H. K., & Murrin, L. C. (1995). In situ hybridization analysis of CHOT1, a creatine transporter, in the rat central nervous system. Journal of Comparative Neurology, 351(1), 94-103. Pasquali, M., Schwarz, E., Jensen, M., Yuzyuk, T., DeBiase, I., Randall, H., & Longo, N. (2014). Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT) deficiency. Journal of Inherited Metabolic Disease, 37(2), 231-236. Dodd, J. R., & Christie, D. L. (2007). Selective amino acid substitutions convert the creatine transporter to a γ-aminobutyric acid transporter. Journal of Biological Chemistry, 282(21), 15528-15533. Carling, R. S., Hogg, S. L., Wood, T. C., & Calvin, J. (2008). Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 45(6), 575-584. El-Gharbawy, A. H., Goldstein, J. L., Millington, D. S., Vaisnins, A. E., Schlune, A., Barshop, B. A., Schulze, A., Koeberl, D. D., & Young, S. P. (2013). Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency. Molecular Genetics and Metabolism, 109(2), 215-217. Kleefstra, T., Rosenberg, E., Salomons, G., Stroink, H., Van Bokhoven, H., Hamel, B., & De Vries, B. (2005). Progressive intestinal, neurological and psychiatric problems in two adult males with cerebral creatine deficiency caused by an SLC6A8 mutation. Clinical Genetics, 68(4), 379-381. Arias, A., Garcia-Villoria, J., & Ribes, A. (2004). Guanidinoacetate and creatine/creatinine levels in controls and patients with urea cycle defects. Molecular Genetics and Metabolism, 82(3), 220-223. Cheillan, D., Curt, M. J.-C., Briand, G., Salomons, G. S., Mention-Mulliez, K., Dobbelaere, D., Cuisset, J.-M., Lion-François, L., Portes, V. D., Chabli, A., Valayannopoulos, V., Benoist, J.-F., Pinard, J.-M., Simard, G., Douay, O., Deiva, K., Afenjar, A., Héron, D., Rivier, F., … Vamecq, J. (2012). Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms. Orphanet Journal of Rare Diseases, 7(1). Daly, M. M. (1985). Guanidinoacetate methyltransferase activity in tissues and cultured cells. Archives of Biochemistry and Biophysics, 236(2), 576-584. Carducci, C., Birarelli, M., Santagata, P., Leuzzi, V., Carducci, C., & Antonozzi, I. (2001). Automated high-performance liquid chromatographic method for the determination of guanidinoacetic acid in dried blood spots: A tool for early diagnosis of guanidinoacetate methyltransferase deficiency. Journal of Chromatography B: Biomedical Sciences and Applications, 755(1-2), 343-348. Young, S., Struys, E., & Wood, T. (2007). Quantification of creatine and guanidinoacetate using GC-MS and LC-MS/MS for the detection of cerebral creatine deficiency syndromes. Current Protocols in Human Genetics, 54(1). Mørkrid, L., Rowe, A. D., Elgstoen, K. B. P., Olesen, J. H., Ruijter, G., Hall, P. L., Tortorelli, S., Schulze, A., Kyriakopoulou, L., Wamelink, M. M. C., van de Kamp, J. M., Salomons, G. S., & Rinaldo, P. (2015). Continuous age- and sex-adjusted reference intervals of urinary markers for cerebral creatine deficiency syndromes: A novel approach to the definition of reference intervals. Clinical Chemistry, 61(5), 760-768. Peral, M. J., Vázquez-Carretero, M. D., & Ilundain, A. A. (2010). Na+/Cl−/creatine transporter activity and expression in rat brain synaptosomes. Neuroscience, 165(1), 53-60. Torremans, A., Marescau, B., Possemiers, I., Van Dam, D., D'Hooge, R., Isbrandt, D., & De Deyn, P. P. (2005). Biochemical and behavioural phenotyping of a mouse model for GAMT deficiency. Journal of the Neurological Sciences, 231(1-2), 49-55. Pyne-Geithman, G. J., deGrauw, T. J., Cecil, K. M., Chuck, G., Lyons, M. A., Ishida, Y., & Clark, J. F. (2004). Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: A case study. Molecular and Cellular Biochemistry, 262(1-2), 35-39. Hunneman, D. H., & Hanefeld, F. (1997). GC-MS determination of guanidinoacetate in urine and plasma. Journal of Inherited Metabolic Disease, 20(3), 450-452. Valongo, C., Cardoso, M. L., Domingues, P., Almeida, L., Verhoeven, N., Salomons, G., Jakobs, C., & Vilarinho, L. (2004). Age related reference values for urine creatine and guanidinoacetic acid concentration in children and adolescents by gas chromatography–mass spectrometry. Clinica Chimica Acta, 348(1-2), 155-161. Arias, A., Ormazabal, A., Moreno, J., González, B., Vilaseca, M. A., García-Villoria, J., Pàmpols, T., Briones, P., Artuch, R., & Ribes, A. (2006). Methods for the diagnosis of creatine deficiency syndromes: A comparative study. Journal of Neuroscience Methods, 156(1-2), 305-309. Viau, K. S., Ernst, S. L., Pasquali, M., Botto, L. D., Hedlund, G., & Longo, N. (2013). Evidence-based treatment of guanidinoacetate methyltransferase (GAMT) deficiency. Molecular Genetics and Metabolism, 110(3), 255-262. Verhoeven, N. M., Roos, B., Struys, E. A., Salomons, G. S., van der Knaap, M. S., & Jakobs, C. (2004). Enzyme assay for diagnosis of guanidinoacetate methyltransferase deficiency. Clinical Chemistry, 50(2), 441-443. Comeaux, M. S., Wang, J., Wang, G., Kleppe, S., Zhang, V. W., Schmitt, E. S., Craigen, W. J., Renaud, D., Sun, Q., & Wong, L.-J. (2013). Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 109(3), 260-268. Hanna-El-Daher, L., Béard, E., Henry, H., Tenenbaum, L., & Braissant, O. (2015). Mild guanidinoacetate increase under partial guanidinoacetate methyltransferase deficiency strongly affects brain cell development. Neurobiology of Disease, 79, 14-27. Schulze, A., Mayatepek, E., Bachert, P., Marescau, B., De Deyn, P. P., & Rating, D. (1998). Therapeutic trial of arginine restriction in creatine deficiency syndrome. European Journal of Pediatrics, 157(7), 606-607. Verbruggen, K. T., Sijens, P. E., Schulze, A., Lunsing, R. J., Jakobs, C., Salomons, G. S., & van Spronsen, F. J. (2007). Successful treatment of a guanidinoacetate methyltransferase deficient patient: Findings with relevance to treatment strategy and pathophysiology. Molecular Genetics and Metabolism, 91(3), 294-296. Ndika, J. D. T., Johnston, K., Barkovich, J. A., Wirt, M. D., O'Neill, P., Betsalel, O. T., Jakobs, C., & Salomons, G. S. (2012). Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. Molecular Genetics and Metabolism, 106(1), 48-54. Khaikin, Y., Sidky, S., Abdenur, J., Anastasi, A., Ballhausen, D., Buoni, S., Chan, A., Cheillan, D., Dorison, N., Goldenberg, A., Goldstein, J., Hofstede, F. C., Jacquemont, M.-L., Koeberl, D. D., Lion-Francois, L., Lund, A. M., Mention, K., Mundy, H., O'Rourke, D., … Mercimek-Andrews, S. (2018). Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. European Journal of Paediatric Neurology, 22(3), 369-379. Van Pilsum, J. F., Olsen, B., Taylor, D., Rozycki, T., & Pierce, J. C. (1963). Transamidinase activities, in vitro, of tissues from various mammals and from rats fed protein-free, creatine-supplemented and normal diets. Archives of Biochemistry and Biophysics, 100(3), 520-524. Guimbal, C., & Kilimann, M. W. (1994). A creatine transporter CDNA from Torpedo illustrates structure/function relationships in the GABA/noradrenaline transporter family. Journal of Molecular Biology, 241(2), 317-324. Betsalel, O. T., Pop, A., Rosenberg, E. H., Fernandez-Ojeda, M., Jakobs, C., & Salomons, G. S. (2012). Detection of variants in SLC6A8 and functional analysis of unclassified missense variants. Molecular Genetics and Metabolism, 105(4), 596-601. DesRoches, C.-L., Patel, J., Wang, P., Minassian, B., Salomons, G. S., Marshall, C. R., & Mercimek-Mahmutoglu, S. (2015). Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene. Gene, 565(2), 187-191. Sharer, J. D., Bodamer, O., Longo, N., Tortorelli, S., Wamelink, M. M. C., & Young, S. (2017). Laboratory diagnosis of creatine deficiency syndromes: A technical standard and guideline of the American College of Medical Genetics and Genomics. Genetics in Medicine, 19(2), 256-263. Bottomley, P. A., Edelstein, W. A., Hart, H. R., Schenck, J. F., & Smith, L. S. (1984). Spatial localization in 31P and 13C NMR spectroscopy in vivo using surface coils. Magnetic Resonance in Medicine, 1(3), 410-413. Chen, L., Wei, Z., Cai, S., Li, Y., Liu, G., Lu, H., Weiss, R. G., van Zijl, P. C. M., & Xu, J. (2019). High-resolution creatine mapping of mouse brain at 11.7 T using non-steady-state chemical exchange saturation transfer. NMR in Biomedicine, 32(11). Joncquel-Chevalier Curt, M., Cheillan, D., Briand, G., Salomons, G. S., Mention-Mulliez, K., Dobbelaere, D., Cuisset, J.-M., Lion-François, L., Des Portes, V., Chabli, A., Valayannopoulos, V., Benoist, J.-F., Pinard, J.-M., Simard, G., Douay, O., Deiva, K., Tardieu, M., Afenjar, A., Héron, D., … Vamecq, J. (2013). Creatine and guanidinoacetate reference values in a French population. Molecular Genetics and Metabolism, 110(3), 263-267. Udobi, K. C., Kokenge, A. N., Hautman, E. R., Ullio, G., Coene, J., Williams, M. T., Vorhees, C. V., Mabondzo, A., & Skelton, M. R. (2018). Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8. Genes, Brain and Behavior, 17(6). Sandoval, N., Bauer, D., Brenner, V., Coy, J. F., Drescher, B., Kioschis, P., Korn, B., Nyakatura, G., Poustka, A., Reichwald, K., Rosenthal, A., & Platzer, M. (1996). The genomic organization of a human creatine transporter (CRTR) gene located in Xq28. Genomics, 35(2), 383-385. Baker, S. A., Gajera, C. R., Wawro, A. M., Corces, M. R., & Montine, T. J. (2021). GATM and GAMT synthesize creatine locally throughout the mammalian body and within oligodendrocytes of the brain. Brain Research, 1770, 147627. Nouioua, S., Cheillan, D., Zaouidi, S., Salomons, G. S., Amedjout, N., Kessaci, F., Boulahdour, N., Hamadouche, T., & Tazir, M. (2013). Creatine deficiency syndrome. A treatable myopathy due to arginine–glycine amidinotransferase (AGAT) deficiency. Neuromuscular Disorders, 23(8), 670-674. Russell, A. P., Ghobrial, L., Wright, C. R., Lamon, S., Brown, E. L., Kon, M., Skelton, M. R., & Snow, R. J. (2014). Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle. Frontiers in Physiology, 5. Betsalel, O. T., van de Kamp, J. M., Martínez-Muñoz, C., Rosenberg, E. H., de Brouwer, A. P. M., Pouwels, P. J. W., van der Knaap, M. S., Mancini, G. M. S., Jakobs, C., Hamel, B. C. J., & Salomons, G. S. (2008). Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency. neurogenetics, 9(3), 183-190. Trotier-Faurion, A., Dézard, S., Taran, F., Valayannopoulos, V., de Lonlay, P., & Mabondzo, A. (2013). Synthesis and biological evaluation of New creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency. Journal of Medicinal Chemistry, 56(12), 5173-5181. Ullio-Gamboa, G., Udobi, K. C., Dezard, S., Perna, M. K., Miles, K. N., Costa, N., Taran, F., Pruvost, A., Benoit, J.-P., Skelton, M. R., Lonlay, P. D., & Mabondzo, A. (2019). Dodecyl creatine ester-loaded nanoemulsion as a promising therapy for creatine transporter deficiency. Nanomedicine, 14(12), 1579-1593. Walker, J. B. (1958). Role for pancreas in biosynthesis of creatine. Experimental Biology and Medicine, 98(1), 7-9. Humm, A., Fritsche, E., Mann, K., Göhl, M., & Huber, R. (1997). Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue. Biochemical Journal, 322(3), 771-776. Cecil, K. M., DeGrauw, T. J., Salomons, G. S., Jakobs, C., Egelhoff, J. C., & Clark, J. F. (2003). Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency. Journal of Computer Assisted Tomography, 27(1), 44-47. Duran-Trio, L., Fernandes-Pires, G., Simicic, D., Grosse, J., Roux-Petronelli, C., Bruce, S. J., Binz, P.-A., Sandi, C., Cudalbu, C., & Braissant, O. (2021). A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism. Scientific Reports, 11(1). Ogawa, H., Date, T., Gomi, T., Konishi, K., Pitot, H. C., Cantoni, G. L., & Fujioka, M. (1988). Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver. Proceedings of the National Academy of Sciences, 85(3), 694-698. Morris, A. A. M., Appleton, R. E., Power, B., Isherwood, D. M., Abernethy, L. J., Taylor, R. W., Turnbull, D. M., Verhoeven, N. M., Salomons, G. S., & Jakobs, C. (2007). Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy. Journal of Inherited Metabolic Disease, 30(1), 100-100. Sijens, P. E., Verbruggen, K. T., Oudkerk, M., van Spronsen, F. J., & Soorani-Lunsing, R. J. (2005). 1H MR spectroscopy of the brain in Cr transporter defect. Molecular Genetics and Metabolism, 86(3), 421-422. Dezortova, M., Jiru, F., Petrasek, J., Malinova, V., Zeman, J., Jirsa, M., & Hajek, M. (2008). 1H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency. Magnetic Resonance Materials in Physics, Biology and Medicine, 21(5), 327-332. van de Kamp, J. M., Errami, A., Howidi, M., Anselm, I., Winter, S., Phalin-Roque, J., Osaka, H., van Dooren, S. J. M., Mancini, G. M., Steinberg, S. J., & Salomons, G. S. (2015). Genotype–phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1. Clinical Genetics, 87(2), 141-147. Jomura, R., Akanuma, S.-I., Tachikawa, M., & Hosoya, K.-I. (2022). SLC6A and SLC16A family of transporters: Contribution to transport of creatine and creatine precursors in creatine biosynthesis and distribution. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1864(3), 183840. Singh, A., Debnath, A., Cai, K., Bagga, P., Haris, M., Hariharan, H., & Reddy, R. (2019). Evaluating the feasibility of creatine-weighted CEST MRI in human brain at 7 T using a Z-spectral fitting approach. NMR in Biomedicine, 32(12). Mercimek-Mahmutoglu, S., Sinclair, G., van Dooren, S. J. M., Kanhai, W., Ashcraft, P., Michel, O. J., Nelson, J., Betsalel, O. T., Sweetman, L., Jakobs, C., & Salomons, G. S. (2012). Guanidinoacetate methyltransferase deficiency: First steps to newborn screening for a treatable neurometabolic disease. Molecular Genetics and Metabolism, 107(3), 433-437. Komoto, J., Huang, Y., Takata, Y., Yamada, T., Konishi, K., Ogawa, H., Gomi, T., Fujioka, M., & Takusagawa, F. (2002). Crystal structure of guanidinoacetate methyltransferase from rat liver: A model structure of protein arginine methyltransferase. Journal of Molecular Biology, 320(2), 223-235. van de Kamp, J. M., Jakobs, C., Gibson, K. M., & Salomons, G. S. (2013). New insights into creatine transporter deficiency: The importance of recycling creatine in the brain. Journal of Inherited Metabolic Disease, 36(1), 155-156. Zhang, Z., Wang, K., Park, S., Li, A., Li, Y., Weiss, R. G., & Xu, J. (2023). The exchange rate of creatine CEST in mouse brain. Magnetic Resonance in Medicine, 90(2), 373-384. Anselm, I. A., Coulter, D. L., & Darras, B. T. (2008). Cardiac manifestations in a child with a novel mutation in creatine transporter gene slc6a8. Neurology, 70(18), 1642-1644. Mercimek-Mahmutoglu, S., Pop, A., Kanhai, W., Fernandez Ojeda, M., Holwerda, U., Smith, D., Loeber, J. G., Schielen, P. C. J. I., & Salomons, G. S. (2016). A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene. Gene, 575(1), 127-131. Trotier-Faurion, A., Passirani, C., Béjaud, J., Dézard, S., Valayannopoulos, V., Taran, F., de Lonlay, P., Benoit, J.-P., & Mabondzo, A. (2015). Dodecyl creatine ester and lipid nanocapsule: A double strategy for the treatment of creatine transporter deficiency. Nanomedicine, 10(2), 185-191. Manos, P., & Bryan, G. K. (1994). Cellular and subcellular compartmentation of creatine kinase in brain. Developmental Neuroscience. Borsook, H., & Dubnoff, J. W. (1940). The synthesis of glycocyamine in rat kidney and a mechanism of creatine synthesis in vivo. Science, 91(2371), 551-552. Walker, J. B. (1963). Formamidine group transfer in extracts of human pancreas, liver, and kidney. Biochimica et Biophysica Acta, 73(2), 241-247. Sijens, P. E., Verbruggen, K. T., Meiners, L. C., Soorani-Lunsing, R. J., Rake, J. P., & Oudkerk, M. (2005). 1H chemical shift imaging of the brain in guanidino methyltransferase deficiency, a creatine deficiency syndrome; Guanidinoacetate accumulation in the gray matter. European Radiology, 15(9), 1923-1926. Verbruggen, K. T., Meiners, L. C., Sijens, P. E., Lunsing, R. J., van Spronsen, F. J., & Brouwer, O. F. (2009). Magnetic resonance imaging and proton magnetic resonance spectroscopy of the brain in the diagnostic evaluation of developmental delay. European Journal of Paediatric Neurology, 13(2), 181-190. O’rourke, D. J., Ryan, S., Salomons, G., Jakobs, C., Monavari, A., & King, M. D. (2009). Guanidinoacetate methyltransferase (GAMT) deficiency: Late onset of movement disorder and preserved expressive language. Developmental Medicine & Child Neurology, 51(5), 404-407. Hautman, E. R., Kokenge, A. N., Udobi, K. C., Williams, M. T., Vorhees, C. V., & Skelton, M. R. (2014). Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits. Journal of Inherited Metabolic Disease, 37(1), 63-68. Fons, C., Arias, A., Sempere, A., Póo, P., Pineda, M., Mas, A., López-Sala, A., Garcia-Villoria, J., Vilaseca, M. A., Ozaez, L., Lluch, M., Artuch, R., Campistol, J., & Ribes, A. (2010). Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency. Molecular Genetics and Metabolism, 99(3), 296-299. Borsook, H., & Dubnoff, J. W. (1945). Methylation of guanidoacetic acid by homocystine plus choline with rat liver slices. Journal of Biological Chemistry, 160(2), 635-636. Colas, C., Banci, G., Martini, R., & Ecker, G. F. (2020). Studies of structural determinants of substrate binding in the creatine transporter (CreaT, SLC6A8) using molecular models. Scientific Reports, 10(1). Schiaffino, M. C., Bellini, C., Costabello, L., Caruso, U., Jakobs, C., Salomons, G. S., & Bonioli, E. (2005). X-linked creatine transporter deficiency: Clinical description of a patient with a novel SLC6A8 gene mutation. Neurogenetics, 6(3), 165-168. Desroches, C.-L., Patel, J., Wang, P., Minassian, B., Marshall, C. R., Salomons, G. S., & Mercimek-Mahmutoglu, S. (2015). Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene. Molecular Genetics and Genomics, 290(6), 2163-2171. Mercimek-Mahmutoglu, S., Muehl, A., Salomons, G. S., Neophytou, B., Moeslinger, D., Struys, E., Bodamer, O. A., Jakobs, C., & Stockler-Ipsiroglu, S. (2009). Screening for X-linked creatine transporter (SLC6A8) deficiency via simultaneous determination of urinary creatine to creatinine ratio by tandem mass-spectrometry. Molecular Genetics and Metabolism, 96(4), 273-275. Engelke, U. F. H., Tassini, M., Hayek, J., de Vries, M., Bilos, A., Vivi, A., Valensin, G., Buoni, S., Zannolli, R., Brussel, W., Kremer, B., Salomons, G. S., Veendrick-Meekes, M. J. B. M., Kluijtmans, L. A. J., Morava, É., & Wevers, R. A. (2009). Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids. NMR in Biomedicine, 22(5), 538-544. Kan, H. E., Meeuwissen, E., van Asten, J. J., Veltien, A., Isbrandt, D., & Heerschap, A. (2007). Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy. Journal of Applied Physiology, 102(6), 2121-2127. Jaggumantri, S., Dunbar, M., Edgar, V., Mignone, C., Newlove, T., Elango, R., Collet, J. P., Sargent, M., Stockler-Ipsiroglu, S., & van Karnebeek, C. D. M. (2015). Treatment of creatine transporter (SLC6A8) deficiency with oral S-adenosyl methionine as adjunct to L-arginine, glycine, and creatine supplements. Pediatric Neurology, 53(4), 360-363.e2. Humm, A., Huber, R., & Mann, K. (1994). The amino acid sequences of human and pig L-arginine:glycine amidinotransferase. FEBS Letters, 339(1-2), 101-107. Almeida, L. S., Vilarinho, L., Darmin, P. S., Rosenberg, E. H., Martinez-Muñoz, C., Jakobs, C., & Salomons, G. S. (2007). A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Molecular Genetics and Metabolism, 91(1), 1-6. Schulze, A., Bauman, M., Tsai, A. C.-H., Reynolds, A., Roberts, W., Anagnostou, E., Cameron, J., Nozzolillo, A. A., Chen, S., Kyriakopoulou, L., Scherer, S. W., & Loh, A. (2016). Prevalence of creatine deficiency syndromes in children with nonsyndromic autism. Pediatrics, 137(1). Chen, H.-R., Zhang-Brotzge, X., Morozov, Y. M., Li, Y., Wang, S., Zhang, H. H., Kuan, I. S., Fugate, E. M., Mao, H., Sun, Y.-Y., Rakic, P., Lindquist, D. M., DeGrauw, T., & Kuan, C.-Y. (2021). Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis. JCI Insight, 6(17). Mercimek-Mahmutoglu, S., Dunbar, M., Friesen, A., Garret, S., Hartnett, C., Huh, L., Sinclair, G., Stockler, S., Wellington, S., Pouwels, P. J. W., Salomons, G. S., & Jakobs, C. (2012). Evaluation of two year treatment outcome and limited impact of arginine restriction in a patient with GAMT deficiency. Molecular Genetics and Metabolism, 105(1), 155-158. Dodd, J. R., Birch, N. P., Waldvogel, H. J., & Christie, D. L. (2010). Functional and immunocytochemical characterization of the creatine transporter in rat hippocampal neurons. Journal of Neurochemistry, 115(3), 684-693. Verhoeven, N. M., Schor, D. S. M., Roos, B., Battini, R., Stöckler-Ipsiroglu, S., Salomons, G. S., & Jakobs, C. (2003). Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-arginine:glycine amidinotransferase deficiency. Clinical Chemistry, 49(5), 803-805. Gross, M. D., Eggen, M. A., Simon, A. M., & Van Pilsum, J. F. (1986). The purification and characterization of human kidney L-arginine:glycine amidinotransferase. Archives of Biochemistry and Biophysics, 251(2), 747-755. Wang, L., Zhang, Y., Shao, M., & Zhang, H. (2007). Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. The International Journal of Developmental Biology, 51(3), 247-253. Wang, K., Huang, J., Ju, L., Xu, S., Gullapalli, R. P., Liang, Y., Rogers, J., Li, Y., van Zijl, P. C. M., Weiss, R. G., Chan, K. W. Y., & Xu, J. (2024). Creatine mapping of the brain at 3T by CEST MRI. Magnetic Resonance in Medicine, 91(1), 51-60. Salazar, M. D., Zelt, N. B., Saldivar, R., Kuntz, C. P., Chen, S., Penn, W. D., Bonneau, R., Koehler Leman, J., & Schlebach, J. P. (2020). Classification of the molecular defects associated with pathogenic variants of the SLC6A8 creatine transporter. Biochemistry, 59(13), 1367-1377. Sinclair, G. B., van Karnebeek, C. D. M., Ester, M., Boyd, F., Nelson, T., Stockler-Ipsiroglu, S., & Vallance, H. (2016). A three-tier algorithm for guanidinoacetate methyltransferase (GAMT) deficiency newborn screening. Molecular Genetics and Metabolism, 118(3), 173-177. Bian, X., Zhu, J., Jia, X., Liang, W., Yu, S., Li, Z., Zhang, W., & Rao, Y. (2023). Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology. eLife, 12. Udobi, K. C., Delcimmuto, N., Kokenge, A. N., Abdulla, Z. I., Perna, M. K., & Skelton, M. R. (2019). Deletion of the creatine transporter gene in neonatal, but not adult, mice leads to cognitive deficits. Journal of Inherited Metabolic Disease, 42(5), 966-974. Chilosi, A., Casarano, M., Comparini, A., Battaglia, F. M., Mancardi, M. M., Schiaffino, C., Tosetti, M., Leuzzi, V., Battini, R., & Cioni, G. (2012). Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency. Orphanet Journal of Rare Diseases, 7(1). Betsalel, O. T., Rosenberg, E. H., Almeida, L. S., Kleefstra, T., Schwartz, C. E., Valayannopoulos, V., Abdul-Rahman, O., Poplawski, N., Vilarinho, L., Wolf, P., den Dunnen, J. T., Jakobs, C., & Salomons, G. S. (2011). Characterization of novel SLC6A8 variants with the use of splice-site analysis tools and implementation of a newly developed LOVD database. European Journal of Human Genetics, 19(1), 56-63. Mori, A., Katayama, Y., Higashidate, S., & Kimura, S. (1979). Fluorometrical analysis of guanidino compounds in mouse brain. Journal of Neurochemistry, 32(2), 643-644. Steinbusch, L. K. M., Wang, P., Waterval, H. W. A. H., Stassen, F. A. P. M., Coene, K. L. M., Engelke, U. F. H., Habets, D. D. J., Bierau, J., & Körver-Keularts, I. M. L. W. (2021). Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism. Journal of Inherited Metabolic Disease, 44(5), 1113-1123. Molinaro, A., Alessandrì, M. G., Putignano, E., Leuzzi, V., Cioni, G., Baroncelli, L., & Pizzorusso, T. (2019). A nervous system-specific model of creatine transporter deficiency recapitulates the cognitive endophenotype of the disease: A longitudinal study. Scientific Reports, 9(1). Rosko, L. M., Gentile, T., Smith, V. N., Manavi, Z., Melchor, G. S., Hu, J., Shults, N. V., Albanese, C., Lee, Y., Rodriguez, O., & Huang, J. K. (2023). Cerebral creatine deficiency affects the timing of oligodendrocyte myelination. The Journal of Neuroscience, 43(7), 1143-1153. Isbrandt, D., & von Figura, K. (1995). Cloning and sequence analysis of human guanidinoacetate N-methyltransferase cDNA. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1264(3), 265-267. Valayannopoulos, V., Bakouh, N., Mazzuca, M., Nonnenmacher, L., Hubert, L., Makaci, F., Chabli, A., Salomons, G. S., Mellot-Draznieks, C., Brulé, E., de Lonlay, P., Toulhoat, H., Munnich, A., Planelles, G., & de Keyzer, Y. (2013). Functional and electrophysiological characterization of four non-truncating mutations responsible for creatine transporter (SLC6A8) deficiency syndrome. Journal of Inherited Metabolic Disease, 36(1), 103-112. Battini, R., Alessandrì, M. G., Casalini, C., Casarano, M., Tosetti, M., & Cioni, G. (2017). Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. Orphanet Journal of Rare Diseases, 12(1). Wong, T. (1971). Studies on creatine determination by α-naphthol-diacetyl reaction. Analytical Biochemistry, 40(1), 18-28. Verhoeven, N. M., Guérand, W. S., Struys, E. A., Bouman, A. A., van der Knaap, M. S., & Jakobs, C. (2000). Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall. Journal of Inherited Metabolic Disease, 23(8), 835-840. Schulze, A., Tran, C., Levandovskiy, V., Patel, V., & Cortez, M. A. (2016). Systemic availability of guanidinoacetate affects GABAA receptor function and seizure threshold in GAMT deficient mice. Amino Acids, 48(8), 2041-2047. Ghirardini, E., Calugi, F., Sagona, G., Di Vetta, F., Palma, M., Battini, R., Cioni, G., Pizzorusso, T., & Baroncelli, L. (2021). The role of preclinical models in creatine transporter deficiency: Neurobiological mechanisms, biomarkers and therapeutic development. Genes, 12(8), 1123. Adriano, E., Garbati, P., Damonte, G., Salis, A., Armirotti, A., & Balestrino, M. (2011). Searching for a therapy of creatine transporter deficiency: Some effects of creatine ethyl ester in brain slices in vitro. Neuroscience, 199, 386-393. Newmeyer, A., deGrauw, T., Clark, J., Chuck, G., & Salomons, G. (2007). Screening of male patients with autism spectrum disorder for creatine transporter deficiency. Neuropediatrics, 38(6), 310-312. Mencarelli, M. A., Tassini, M., Pollazzon, M., Vivi, A., Calderisi, M., Falco, M., Fichera, M., Monti, L., Buoni, S., Mari, F., Engelke, U., Wevers, R. A., Hayek, J., & Renieri, A. (2011). Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability. American Journal of Medical Genetics Part A, 155(10), 2446-2452. Meera, P., Uusi-Oukari, M., Wallner, M., & Lipshutz, G. S. (2023). Guanidinoacetate (GAA) is a potent GABAA receptor GABA mimetic: Implications for neurological disease pathology. Journal of Neurochemistry, 165(3), 445-454. Fons, C., Sempere, Á., Sanmartí, F. X., Arias, Á., Póo, P., Pineda, M., Ribes, A., Merinero, B., Vilaseca, M. A., Salomons, G. S., Artuch, R., & Campistol, J. (2009). Epilepsy spectrum in cerebral creatine transporter deficiency. Epilepsia, 50(9), 2168-2170. Mikati, A. G., Gheida, I. A., Shamseddine, A., Mikati, M. A., & Karam, P. E. (2013). Epileptic and electroencephalographic manifestations of guanidinoacetate-methyltransferase deficiency. Epileptic Disorders, 15(4), 407-416. Haas, D., Gan-Schreier, H., Langhans, C.-D., Anninos, A., Haege, G., Burgard, P., Schulze, A., Hoffmann, G. F., & Okun, J. G. (2014). Diagnosis and therapeutic monitoring of inborn errors of creatine metabolism and transport using liquid chromatography–tandem mass spectrometry in urine, plasma and CSF. Gene, 538(1), 188-194. Ghirardini, E., Sagona, G., Marquez-Galera, A., Calugi, F., Navarron, C. M., Cacciante, F., Chen, S., Di Vetta, F., Dadà, L., Mazziotti, R., Lupori, L., Putignano, E., Baldi, P., Lopez-Atalaya, J. P., Pizzorusso, T., & Baroncelli, L. (2023). Cell-specific vulnerability to metabolic failure: The crucial role of parvalbumin expressing neurons in creatine transporter deficiency. Acta Neuropathologica Communications, 11(1). Walker, J. B. (1963). End-product repression in the creatine pathway of the developing chick embryo. Advances in Enzyme Regulation, 1, 151-168. Carducci, C., Carducci, C., Santagata, S., Adriano, E., Artiola, C., Thellung, S., Gatta, E., Robello, M., Florio, T., Antonozzi, I., Leuzzi, V., & Balestrino, M. (2012). In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism. BMC Neuroscience, 13(1). Cupello, A., Balestrino, M., Gatta, E., Pellistri, F., Siano, S., & Robello, M. (2008). Activation of cerebellar granule cells GABAA receptors by guanidinoacetate. Neuroscience, 152(1), 65-69. Abdulla, Z. I., Pennington, J. L., Gutierrez, A., & Skelton, M. R. (2020). Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness. Behavioural Brain Research, 377, 112254. Mazziotti, R., Cacciante, F., Sagona, G., Lupori, L., Gennaro, M., Putignano, E., Alessandrì, M. G., Ferrari, A., Battini, R., Cioni, G., Pizzorusso, T., & Baroncelli, L. (2020). Novel translational phenotypes and biomarkers for creatine transporter deficiency. Brain Communications, 2(2). Duran-Trio, L., Fernandes-Pires, G., Grosse, J., Soro-Arnaiz, I., Roux-Petronelli, C., Binz, P., De Bock, K., Cudalbu, C., Sandi, C., & Braissant, O. (2022). Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy. Journal of Inherited Metabolic Disease, 45(2), 278-291. Verma, A. (2010). Arginine:glycine amidinotransferase deficiency: A treatable metabolic encephalomyopathy. Neurology, 75(2), 186-188. Lohmann, K. (1934). Über den Chemismus der Muskelkontraktion. Die Naturwissenschaften, 22(22-24), 409-411. Sempere, A., Fons, C., Arias, A., Rodríguez-Pombo, P., Colomer, R., Merinero, B., Alcaide, P., Capdevila, A., Ribes, A., Artuch, R., & Campistol, J. (2009). Creatine transporter deficiency in two adult patients with static encephalopathy. Journal of Inherited Metabolic Disease, 32(S1), 91-96. Miller, J. S., Thomas, R. P., Bennett, A., Bianconi, S., Bruchey, A., Davis, R. J., Ficicioglu, C., Guthrie, W., Porter, F. D., & Thurm, A. (2019). Early indicators of creatine transporter deficiency. The Journal of Pediatrics, 206, 283-285. Auray-Blais, C., Maranda, B., & Lavoie, P. (2014). High-throughput tandem mass spectrometry multiplex analysis for newborn urinary screening of creatine synthesis and transport disorders, Triple H syndrome and OTC deficiency. Clinica Chimica Acta, 436, 249-255. Hart, K., Rohrwasser, A., Wallis, H., Golsan, H., Shao, J., Anderson, T., Wang, X., Szabo-Fresnais, N., Morrissey, M., Kay, D. M., Wojcik, M., Galvin-Parton, P. A., Longo, N., Caggana, M., & Pasquali, M. (2021). Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency. Molecular Genetics and Metabolism, 134(1-2), 60-64. Abdulla, Z. I., Pahlevani, B., Lundgren, K. H., Pennington, J. L., Udobi, K. C., Seroogy, K. B., & Skelton, M. R. (2020). Deletion of the creatine transporter (Slc6a8) in dopaminergic neurons leads to hyperactivity in mice. Journal of Molecular Neuroscience, 70(1), 102-111. Mercimek-Mahmutoglu, S., Salomons, G. S., & Chan, A. (2014). Case study for the evaluation of current treatment recommendations of guanidinoacetate methyltransferase deficiency: Ineffectiveness of sodium benzoate. Pediatric Neurology, 51(1), 133-137. Cacciante, F., Gennaro, M., Sagona, G., Mazziotti, R., Lupori, L., Cerri, E., Putignano, E., Butt, M., Do, M.-H. T., McKew, J. C., Alessandrì, M. G., Battini, R., Cioni, G., Pizzorusso, T., & Baroncelli, L. (2020). Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of creatine transporter deficiency. Scientific Reports, 10(1). Renema, W. K. J., Kan, H. E., Wieringa, B., & Heerschap, A. (2007). In vivo magnetic resonance spectroscopy of transgenic mouse models with altered high-energy phosphoryl transfer metabolism. NMR in Biomedicine, 20(4), 448-467. Wang, K., Ju, L., Song, Y., Blair, L., Xie, K., Liu, C., Li, A. M., Zhu, D., Xu, F., Liu, G., Heo, H., Yadav, N. N., Oeltzschner, G., Edden, R. A. E., Qin, Q., Kamson, D. O., & Xu, J. (2024). Whole-cerebrum guanidino and amide CEST mapping at 3 T by a 3D stack-of-spirals gradient echo acquisition. Magnetic Resonance in Medicine, 92(4), 1456-1470. Ferrada, E., Wiedmer, T., Wang, W.-A., Frommelt, F., Steurer, B., Klimek, C., Lindinger, S., Osthushenrich, T., Garofoli, A., Brocchetti, S., Bradberry, S., Huang, J., MacNamara, A., Scarabottolo, L., Ecker, G. F., Malarstig, A., & Superti-Furga, G. (2024). Experimental and computational analysis of newly identified pathogenic mutations in the creatine transporter SLC6A8. Journal of Molecular Biology, 436(2), 168383. Thurm, A., Himelstein, D., D'Souza, P., Rennert, O., Jiang, S., Olatunji, D., Longo, N., Pasquali, M., Swedo, S., Salomons, G. S., & Carrillo, N. (2016). Creatine transporter deficiency: Screening of males with neurodevelopmental disorders and neurocognitive characterization of a case. Journal of Developmental & Behavioral Pediatrics, 37(4), 322-326. Bahl, S., Cordeiro, D., MacNeil, L., Schulze, A., & Mercimek-Andrews, S. (2020). Urine creatine metabolite panel as a screening test in neurodevelopmental disorders. Orphanet Journal of Rare Diseases, 15(1). Ream, M. A., Lam, W. K. K., Grosse, S. D., Ojodu, J., Jones, E., Prosser, L. A., Rose, A. M., Comeau, A. M., Tanksley, S., Powell, C. M., & Kemper, A. R. (2023). Evidence and recommendation for guanidinoacetate methyltransferase deficiency newborn screening. Pediatrics, 152(2). Adriano, E., Garbati, P., Salis, A., Damonte, G., Millo, E., & Balestrino, M. (2017). Creatine salts provide neuroprotection even after partial impairment of the creatine transporter. Neuroscience, 340, 299-307. Fritsche, E., Humm, A., & Huber, R. (1997). Substrate binding and catalysis by L-arginine:glycine amidinotransferase — a mutagenesis and crystallographic study. European Journal of Biochemistry, 247(2), 483-490. Farr, C. V., El-Kasaby, A., Erdem, F. A., Sucic, S., Freissmuth, M., & Sandtner, W. (2022). Cooperative binding of substrate and ions drives forward cycling of the human creatine transporter-1. Frontiers in Physiology, 13. Levin, M. D., Bianconi, S., Smith, A., Cawley, N. X., Do, A. D., Hammond, D., Grafstein, J. F., Thurm, A., Miller, J., Perreault, J., Noguchi, A., Springer, D., Kozel, B. A., Spurney, C. F., Wassif, C. A., Yu, Z.-X., Schulze, A., Porter, F. D., & Hannah-Shmouni, F. (2021). X-linked creatine transporter deficiency results in prolonged QTc and increased sudden death risk in humans and disease model. Genetics in Medicine, 23(10), 1864-1872. Modi, B. P., Khan, H. N., van der Lee, R., Wasim, M., Haaxma, C. A., Richmond, P. A., Drögemöller, B., Shah, S., Salomons, G., van der Kloet, F. M., Vaz, F. M., van der Crabben, S. N., Ross, C. J., Wasserman, W. W., van Karnebeek, C. D. M., & Awan, F. R. (2021). Adult GAMT deficiency: A literature review and report of two siblings. Molecular Genetics and Metabolism Reports, 27, 100761. Stockebrand, M., Nejad, A. S., Neu, A., Kharbanda, K. K., Sauter, K., Schillemeit, S., Isbrandt, D., & Choe, C.-U. (2016). Transcriptomic and metabolic analyses reveal salvage pathways in creatine-deficient AGAT−/− mice. Amino Acids, 48(8), 2025-2039. Adriano, E., Gulino, M., Arkel, M., Salis, A., Damonte, G., Liessi, N., Millo, E., Garbati, P., & Balestrino, M. (2018). Di-acetyl creatine ethyl ester, a new creatine derivative for the possible treatment of creatine transporter deficiency. Neuroscience Letters, 665, 217-223. Khoja, S., Lambert, J., Nitzahn, M., Eliav, A., Zhang, Y., Tamboline, M., Le, C. T., Nasser, E., Li, Y., Patel, P., Zhuravka, I., Lueptow, L. M., Tkachyova, I., Xu, S., Nissim, I., Schulze, A., & Lipshutz, G. S. (2022). Gene therapy for guanidinoacetate methyltransferase deficiency restores cerebral and myocardial creatine while resolving behavioral abnormalities. Molecular Therapy - Methods & Clinical Development, 25, 278-296. Chae, Y.-J., Chung, C.-E., Kim, B.-J., Lee, M.-H., & Lee, H. (1998). The gene encoding guanidinoacetate methyltransferase (GAMT) maps to human chromosome 19 at band p13.3 and to mouse chromosome 10. Genomics, 49(1), 162-164. Dreha-Kulaczewski, S., Kalscheuer, V., Tzschach, A., Hu, H., Helms, G., Brockmann, K., Weddige, A., Dechent, P., Schlüter, G., Krätzner, R., Ropers, H. H., Gärtner, J., & Zirn, B. (2013). A novel SLC6A8 mutation in a large family with X-linked intellectual disability: Clinical and proton magnetic resonance spectroscopy data of both hemizygous males and heterozygous females. In JIMD Reports - Case and Research Reports, Volume 13 (pp. 91-99). Springer Berlin Heidelberg. Li, J., & Xu, S. (2023). Diagnosis and treatment of X-linked creatine transporter deficiency: Case report and literature review. Brain Sciences, 13(10), 1382. Giusti, L., Molinaro, A., Alessandrì, M. G., Boldrini, C., Ciregia, F., Lacerenza, S., Ronci, M., Urbani, A., Cioni, G., Mazzoni, M. R., Pizzorusso, T., Lucacchini, A., & Baroncelli, L. (2019). Brain mitochondrial proteome alteration driven by creatine deficiency suggests novel therapeutic venues for creatine deficiency syndromes. Neuroscience, 409, 276-289. Mejdahl Nielsen, M., Petersen, E. T., Fenger, C. D., Ørngreen, M. C., Siebner, H. R., Boer, V. O., Považan, M., Lund, A., Grønborg, S. W., & Hammer, T. B. (2023). X-linked creatine transporter (SLC6A8) deficiency in females: Difficult to recognize, but a potentially treatable disease. Molecular Genetics and Metabolism, 140(3), 107694. Hiel, H., Happe, H. K., Warr, W. B., & Morley, B. J. (1996). Regional distribution of a creatine transporter in rat auditory brainstem: An in-situ hybridization study. Hearing Research, 98(1-2), 29-37. Tachikawa, M., Yashiki, A., Akanuma, S.-I., Matsukawa, H., Ide, S., Minami, M., & Hosoya, K.-I. (2018). Astrocytic γ-aminobutyric acid (GABA) transporters mediate guanidinoacetate transport in rat brain. Neurochemistry International, 113, 1-7. Curie, A., Lion-François, L., Valayannopoulos, V., Perreton, N., Gavanon, M., Touil, N., Brun-Laurisse, A., Gheurbi, F., Buchy, M., Halep, H., Cheillan, D., Mercier, C., Brassier, A., Desnous, B., Kassai, B., De Lonlay, P., & Des Portes, V. (2024). Clinical characteristics, developmental trajectory, and caregiver burden of patients with creatine transporter deficiency ( SLC6A8 ). Neurology, 102(8). Mathis, D., Beese, K., Rüegg, C., Plecko, B., & Hersberger, M. (2020). LC-MS/MS method for the differential diagnosis of treatable early onset inherited metabolic epilepsies. Journal of Inherited Metabolic Disease, 43(5), 1102-1111. Vallance, H., Sinclair, G., Rakic, B., & Stockler-Ipsiroglu, S. (2021). Diagnostic yield from routine metabolic screening tests in evaluation of global developmental delay and intellectual disability. Paediatrics & Child Health, 26(6), 344-348. Nota, B., Ndika, J. D. T., van de Kamp, J. M., Kanhai, W. A., van Dooren, S. J. M., van de Wiel, M. A., Pals, G., & Salomons, G. S. (2014). RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix. Human Mutation, 35(9), 1128-1135. Jensen, M., Müller, C., Schwedhelm, E., Arunachalam, P., Gelderblom, M., Magnus, T., Gerloff, C., Zeller, T., & Choe, C.-U. (2020). Homoarginine- and creatine-dependent gene regulation in murine brains with L-arginine:glycine amidinotransferase deficiency. International Journal of Molecular Sciences, 21(5), 1865. Uemura, T., Ito, S., Masuda, T., Shimbo, H., Goto, T., Osaka, H., Wada, T., Couraud, P.-O., & Ohtsuki, S. (2020). Cyclocreatine transport by SLC6A8, the creatine transporter, in HEK293 cells, a human blood-brain barrier model cell, and CCDSs patient-derived fibroblasts. Pharmaceutical Research, 37(3). Tachikawa, M., Watanabe, M., Fukaya, M., Sakai, K., Terasaki, T., & Hosoya, K.-I. (2018). Cell-type-specific spatiotemporal expression of creatine biosynthetic enzyme S-adenosylmethionine:guanidinoacetate N-methyltransferase in developing mouse brain. Neurochemical Research, 43(2), 500-510. Goldstein, J., Thomas-Wilson, A., Groopman, E., Aggarwal, V., Bianconi, S., Fernandez, R., Hart, K., Longo, N., Liang, N., Reich, D., Wallis, H., Weaver, M., Young, S., & Mercimek-Andrews, S. (2024). ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142(1), 108362. Nedeljkovic, D. D., & Ostojic, S. M. (2024). Biomarkers of creatine metabolism in humans: From plasma to saliva and beyond. Clinical Bioenergetics, 1(1), 2. Garbati, P., Adriano, E., Salis, A., Ravera, S., Damonte, G., Millo, E., & Balestrino, M. (2014). Effects of amide creatine derivatives in brain hippocampal slices, and their possible usefulness for curing creatine transporter deficiency. Neurochemical Research, 39(1), 37-45. Mabondzo, A., Harati, R., Broca-Brisson, L., Guyot, A.-C., Costa, N., Cacciante, F., Putignano, E., Baroncelli, L., Skelton, M. R., Saab, C., Martini, E., Benech, H., Joudinaud, T., Gaillard, J.-C., Armengaud, J., & Hamoudi, R. (2023). Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency. Frontiers in Molecular Neuroscience, 16. Tropak, M. B., Tkachyova, I., Gu, R., Lee, A., & Schulze, A. (2023). Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells. Scientific Reports, 13(1). Pitt, J. J., Tzanakos, N., & Nguyen, T. (2014). Newborn screening for guanidinoacetate methyl transferase deficiency. Molecular Genetics and Metabolism, 111(3), 303-304. Wawro, A. M., Gajera, C. R., Baker, S. A., Nirschl, J. J., Vogel, H., & Montine, T. J. (2021). Creatine transport and pathological changes in creatine transporter deficient mice. Journal of Inherited Metabolic Disease, 44(4), 939-948. Shi, K., Zhao, H., Xu, S., Han, H., & Li, W. (2021). Treatment efficacy of high-dose creatine supplementation in a child with creatine transporter (SLC6A8) deficiency. Molecular Genetics & Genomic Medicine, 9(4). Jenne, D. E., Olsen, A. S., & Zimmer, M. (1997). The human guanidinoacetate methyltransferase (GAMT) gene maps to a syntenic region on 19p13.3, homologous to band C of mouse chromosome 10, but GAMT is not mutated in jittery mice. Biochemical and Biophysical Research Communications, 238(3), 723-727. Clarke, A., Farr, C. V., El-Kasaby, A., Szöllősi, D., Freissmuth, M., Sucic, S., & Stockner, T. (2024). Probing binding and occlusion of substrate in the human creatine transporter-1 by computation and mutagenesis. Protein Science, 33(1). DesRoches, C.-L., Bruun, T., Wang, P., Marshall, C. R., & Mercimek-Mahmutoglu, S. (2016). Arginine-glycine amidinotransferase deficiency and functional characterization of missense variants inGATM: Human mutation. Human Mutation, 37(9), 926-932. Mulik, C., & Mercimek-Andrews, S. (2023). Creatine deficiency disorders: Phenotypes, genotypes, diagnosis, and treatment outcomes. Turkish Archives of Pediatrics, 58(2), 129-135. Wojcik, M., Morrissey, M., Borden, K., Teta, B., Sicko, R., Showers, A., Sunny, S., & Caggana, M. (2022). Method modification to reduce false positives for newborn screening of guanidinoacetate methyltransferase deficiency. Molecular Genetics and Metabolism, 135(3), 186-192. Moravej, H., Inaloo, S., Nahid, S., Mazloumi, S., Nemati, H., Moosavian, T., Nasiri, J., Ghasemi, F., Alaei, M. R., Dalili, S., Aminzadeh, M., Katibeh, P., Amirhakimi, A., Yazdani, N., Ilkhanipoor, H., Afshar, Z., Hadipour, F., & Hadipour, Z. (2023). Inborn errors of metabolism associated with autism among children: A multicenter study from Iran. Indian Pediatrics, 60(3), 193-196. Villar, C., Campistol, J., Fons, C., Armstrong, J., Mas, A., Ormazabal, A., & Artuch, R. (2011). Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients. In JIMD Reports - Case and Research Reports, 2012/1 (pp. 13-16). Springer Berlin Heidelberg. Gorshkov, K., Wang, A. Q., Sun, W., Fisher, E., Frigeni, M., Singleton, M., Thorne, N., Class, B., Huang, W., Longo, N., Do, M. T., Ottinger, E. A., Xu, X., & Zheng, W. (2019). Phosphocyclocreatine is the dominant form of cyclocreatine in control and creatine transporter deficiency patient fibroblasts. Pharmacology Research & Perspectives, 7(6). Adriano, E., Salis, A., Damonte, G., Millo, E., & Balestrino, M. (2022). Effects of delivering guanidinoacetic acid or its prodrug to the neural tissue: Possible relevance for creatine transporter deficiency. Brain Sciences, 12(1), 85. Gechijian, L. N., Muncipinto, G., Rettenmaier, T. J., Labenski, M. T., Rusu, V., Rosskamp, L., Conway, L., van Kalken, D., Gross, L., Iantosca, G., Crotty, W., Mathis, R., Park, H., Rabin, B., Westgate, C., Lyons, M., Deshusses, C., Brandon, N., Brown, D. G., … Barrish, J. C. (2024). Novel corrector for variants of SLC6A8: A therapeutic opportunity for creatine transporter deficiency. ACS Chemical Biology, 19(11), 2372-2382. Passi, G. R., Pandey, S., Devi, A. R. R., Konanki, R., Jain, A. R., Bhatnagar, S., Tripathi, R., & Jain, V. (2022). Cerebral creatine deficiency disorders – a clinical, genetic and follow up study from India. Brain and Development, 44(4), 271-280. Sun, W., Wang, Y., Wu, M., Wu, H., Peng, X., Shi, Y., Xiao, F., Wu, B., Zhou, W., & Lu, W. (2023). Fourteen cases of cerebral creatine deficiency syndrome in children: A cohort study in China. Translational Pediatrics, 12(5), 927-937. Asef, C., Khaksarfard, K., & De Jesús, V. (2016). A non-derivatized assay for the simultaneous detection of amino acids, acylcarnitines, succinylacetone, creatine, and guanidinoacetic acid in dried blood spots via tandem mass spectrometry. International Journal of Neonatal Screening, 2(4), 13. Rossi, L., Nardecchia, F., Pierigè, F., Ventura, R., Carducci, C., Leuzzi, V., Magnani, M., Cabib, S., & Pascucci, T. (2021). Intellectual disability and brain creatine deficit: Phenotyping of the genetic mouse model for GAMT deficiency. Genes, 12(8), 1201. Branovets, J., Karro, N., Barsunova, K., Laasmaa, M., Lygate, C. A., Vendelin, M., & Birkedal, R. (2021). Cardiac expression and location of hexokinase changes in a mouse model of pure creatine deficiency. American Journal of Physiology-Heart and Circulatory Physiology, 320(2), H613-H629. Kale, V. P., Wallery, J., Novak, J., Gibbs, S., Bourdi, M., Do, M.-H. T., McKew, J. C., & Terse, P. S. (2020). Evaluation of chronic toxicity of cyclocreatine, a creatine analog, in Sprague Dawley rat after oral gavage administration for up to 26 weeks. Regulatory Toxicology and Pharmacology, 117, 104750. Schjelderup, J., Hope, S., Vatshelle, C., & van Karnebeek, C. D. M. (2021). Treatment experience in two adults with creatinfe transporter deficiency. Molecular Genetics and Metabolism Reports, 27, 100731. Lygate, C. A., Lake, H. A., McAndrew, D. J., Neubauer, S., & Zervou, S. (2022). Influence of homoarginine on creatine accumulation and biosynthesis in the mouse. Frontiers in Nutrition, 9. Morey, K., Hallinan, B., & Cecil, K. M. (2022). Case report: Clinical and magnetic resonance spectroscopy presentation of a female severely affected with X-linked creatine transporter deficiency. Radiology Case Reports, 17(4), 1115-1119. Li, S., Bianconi, S., van der Veen, J. W., Dang Do, A., Stolinski, J., Cecil, K. M., Hannah-Shmouni, F., Porter, F. D., & Shen, J. (2021). Oxidative phosphorylation in creatine transporter deficiency. NMR in Biomedicine, 34(1). Marten, L. M., Krätzner, R., Salomons, G. S., Fernandez Ojeda, M., Dechent, P., Gärtner, J., Huppke, P., & Dreha-Kulaczewski, S. (2024). Long term follow-up in GAMT deficiency – correlation of therapy regimen, biochemical and in vivo brain proton MR spectroscopy data. Molecular Genetics and Metabolism Reports, 38, 101053. Silvia, C. L., Chandramohan, A., & Palanisamy, S. (2022). Guanidinoacetate methyltransferase deficiency: A treatable cause of developmental delay diagnosed by magnetic resonance spectroscopy. Annals of Indian Academy of Neurology, 25(6), 1196-1198. Yıldız, Y., Ardıçlı, D., Göçmen, R., Yalnızoğlu, D., Topçu, M., Coşkun, T., Tokatlı, A., & Haliloğlu, G. (2024). Electro-clinical features and long-term outcomes in guanidinoacetate methyltransferase (GAMT) deficiency. European Journal of Paediatric Neurology, 49, 66-72. Finezilber, Y., Massey, C., Radley, J. A., & Murphy, E. (2024). Arginine:glycine amidinotransferase (AGAT) deficiency: An easy-to-miss treatable adult-onset myopathy. Practical Neurology, 24(5), 413-416. Benoit, R., Samir, M., Boutin, J., Samuel, A., Brigitte, C., Dominique, D., & Isabelle, R.-V. (2019). LC-MS/MS measurements of urinary guanidinoacetic acid and creatine: Method optimization by deleting derivatization step. Clinica Chimica Acta, 493, 148-155. Marescau, B., Lowenthal, A., Terheggen, H. G., Esmans, E., & Alderweireldt, F. (1982). Guanidino compounds in hyperargininemia. In Urea Cycle Diseases (pp. 427-434). Springer US. Sinha, A., Ahmed, S., George, C., Tsagaris, M., Naufer, A., von Both, I., Tkachyova, I., van Eede, M., Henkelman, M., & Schulze, A. (2020). Magnetic resonance imaging reveals specific anatomical changes in the brain of Agat- and Gamt-mice attributed to creatine depletion and guanidinoacetate alteration. Journal of Inherited Metabolic Disease, 43(4), 827-842. Laasmaa, M., Branovets, J., Barsunova, K., Karro, N., Lygate, C. A., Birkedal, R., & Vendelin, M. (2021). Altered calcium handling in cardiomyocytes from arginine-glycine amidinotransferase-knockout mice is rescued by creatine. American Journal of Physiology-Heart and Circulatory Physiology, 320(2), H805-H825. Hannemann, J., Cordts, K., Seniuk, A., Choe, C.-U., Schmidt-Hutten, L., Duque Escobar, J., Weinberger, F., Böger, R., & Schwedhelm, E. (2021). Arginine:Glycine amidinotransferase is essential for creatine supply in mice during chronic hypoxia. Frontiers in Physiology, 12. Broca-Brisson, L., Harati, R., Disdier, C., Mozner, O., Gaston-Breton, R., Maïza, A., Costa, N., Guyot, A.-C., Sarkadi, B., Apati, A., Skelton, M. R., Madrange, L., Yates, F., Armengaud, J., Hamoudi, R., & Mabondzo, A. (2023). Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency. eLife, 12. Tauer, K., Theile, C., Owens, J. W., Cecil, K. M., & Shillington, A. (2024). Arginine, glycine, and creatine supplementation improves symptoms in a female with creatine transporter deficiency. Psychiatric Genetics, 34(4), 86-90. Fernandes-Pires, G., Azevedo, M. D., Lanzillo, M., Roux-Petronelli, C., Binz, P.-A., Cudalbu, C., Sandi, C., Tenenbaum, L., & Braissant, O. (2024). Rescue of myocytes and locomotion through AAV2/9-2YF intracisternal gene therapy in a rat model of creatine transporter deficiency. Molecular Therapy - Methods & Clinical Development, 32(2), 101251. Broca-Brisson, L., Disdier, C., Harati, R., Hamoudi, R., & Mabondzo, A. (2024). Epigenetic alterations in creatine transporter deficiency: A new marker for dodecyl creatine ester therapeutic efficacy monitoring. Frontiers in Neuroscience, 18. Wells, C., Sorgenfrei, J., Johnson, S. L., Albertson, D., Rutter, J., & Baker, S. A. (2025). Gene delivery of AGAT and GAMT boosts creatine levels in creatine transporter deficiency patient fibroblasts. PLOS One, 20(5), e0319350. Ün, D., Kovalchuk, V., El-Kasaby, A., Kasture, A., Koban, F., Kudlacek, O., Freissmuth, M., & Sucic, S. (2024). Breaking the rules of SLC6 transporters: Export of the human creatine transporter-1 from the endoplasmic reticulum is supported by its N-terminus. Journal of Neurochemistry, 168(9), 2007-2021. Chen, J., Zhang, Y., Chen, N., Ge, J., & Yu, J. (2025). Transport and inhibition mechanisms of human creatine transporter. Cell Discovery, 11(1). Shen, M., Yang, G., Chen, Z., Yang, K., Dong, H., Yin, C., Cheng, Y., Zhang, C., Gu, F., Yang, Y., & Tian, Y. (2022). Identification of novel variations in SLC6A8 and GAMT genes causing cerebral creatine deficiency syndrome. Clinica Chimica Acta, 532, 29-36. Libell, J. L., Lakhani, D. A., Balar, A. B., Khan, M., Carpenter, J. S., & Joseph, J. T. (2023). Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature. Radiology Case Reports, 18(12), 4331-4337. Fortunato, F., De Fiores, R., Sammarra, I., Bonacci, M. C., Caligiuri, M. E., Sturniolo, M., Martino, I., & Gambardella, A. (2025). Focal epilepsy with sensory seizures associated with arginine:glycine amidinotransferase deficiency: A clinical and advanced magnetic resonance imaging study. Epilepsia, 66(7). Berends, L. M., Struys, E. A., Roos, B., Holwerda, U., Jansen, E. E. W., Salomons, G. S., & Wamelink, M. M. C. (2017). Guanidinoacetate methyltransferase activity in lymphocytes, for a fast diagnosis. In JIMD Reports, Volume 37 (pp. 13-17). Springer Berlin Heidelberg. Liu, N., & Sun, Q. (2022). Laboratory diagnosis of cerebral creatine deficiency syndromes by determining creatine and guanidinoacetate in plasma and urine. In Clinical Applications of Mass Spectrometry in Biomolecular Analysis (pp. 129-140). Springer US. Disdier, C., Lhotellier, C., Guyot, A.-C., Costa, N., Théodoro, F., Pruvost, A., Skelton, M. R., Joudinaud, T., Mabondzo, A., & Bénech, H. (2025). Dodecyl creatine ester, a promising treatment to deliver creatine to neurons, achieves pharmacology efficacy in creatine transporter deficiency. European Journal of Medicinal Chemistry, 284, 117195. Farr, C. V., Xiao, Y., El-Kasaby, A., Schupp, M., Hotka, M., di Mauro, G., Clarke, A., Pastor Fernandez, M., Sandtner, W., Stockner, T., Klade, C., Maulide, N., & Freissmuth, M. (2024). Probing the chemical space of guanidino-carboxylic acids to identify the first blockers of the creatine-transporter-1. Molecular Pharmacology, 106(6), 319-333. Flögel, S., Strater, M., Fischer, D., & Gründemann, D. (2025). A creatine efflux transporter in oligodendrocytes. The FEBS Journal, 292(5), 1124-1140. Rajvanshi, N., Bhakat, R., Saxena, S., Rohilla, J., Basu, S., Nandolia, K. K., Agrawal, S., Bhat, N. K., & Chacham, S. (2021). Magnetic resonance spectroscopy in children with developmental delay: Time to look beyond conventional magnetic resonance imaging (MRI). Journal of Child Neurology, 36(6), 440-446. Tise, C. G., Palma, M. J., Cusmano-Ozog, K. P., & Matalon, D. R. (2023). Creatine transporter deficiency presenting as failure to thrive: A case report of a novel SLC6A8 variant causing a treatable but likely underdiagnosed genetic disorder. Journal of Investigative Medicine High Impact Case Reports, 11. Abdennadher, M., Inati, S. K., Rahhal, S., Khan, O., Bartolini, L., Thurm, A., Theodore, W., Miller, J. S., Porter, F. D., & Bianconi, S. (2024). Characterization of seizures and EEG findings in creatine transporter deficiency due to SLC6A8 mutation. American Journal of Medical Genetics Part A, 194(2), 337-345. Joncquel-Chevalier Curt, M., Bout, M.-A., Fontaine, M., Kim, I., Huet, G., Bekri, S., Morin, G., Moortgat, S., Moerman, A., Cuisset, J.-M., Cheillan, D., & Vamecq, J. (2018). Functional assessment of creatine transporter in control and X-linked SLC6A8-deficient fibroblasts. Molecular Genetics and Metabolism, 123(4), 463-471. Pertici, I., D’Angelo, D., Vecellio Reane, D., Reconditi, M., Morotti, I., Putignano, E., Napoli, D., Rastelli, G., Gherardi, G., De Mario, A., Rizzuto, R., Boncompagni, S., Baroncelli, L., Linari, M., Caremani, M., & Raffaello, A. (2025). Creatine transporter (SLC6A8) knockout mice exhibit reduced muscle performance, disrupted mitochondrial Ca2+ homeostasis, and severe muscle atrophy. Cell Death & Disease, 16(1). Wallery, J. J., Kale, V. P., Novak, J., Gibbs, S., Do, M.-H. T., McKew, J. C., & Terse, P. S. (2021). Evaluation of chronic toxicity of cyclocreatine in beagle dogs after oral gavage administration for up to 23 weeks. Toxicology and Applied Pharmacology, 430, 115680. Bianchi, M., Rossi, L., Pierigè, F., De Angeli, P., Aliano, M. P., Carducci, C., Di Carlo, E., Pascucci, T., Nardecchia, F., Leuzzi, V., & Magnani, M. (2022). Engineering new metabolic pathways in isolated cells for the degradation of guanidinoacetic acid and simultaneous production of creatine. Molecular Therapy - Methods & Clinical Development, 25, 26-40. Disdier, C., Soyer, A., Broca-Brisson, L., Goutal, S., Guyot, A.-C., Ziani, N., Breuil, L., Winkeler, A., Hugon, G., Joudinaud, T., Bénech, H., Armengaud, J., Skelton, M. R., Harati, R., Hamoudi, R. A., Tournier, N., & Mabondzo, A. (2024). Impaired brain glucose metabolism as a biomarker for evaluation of dodecyl creatine ester in creatine transporter deficiency: Insights from patient brain-derived organoids and in vivo [18F]FDG PET imaging in a mouse model. Neurobiology of Disease, 202, 106720. Yuan, X., Yin, J., Liu, C., Chen, X., Chen, M., Wang, Y., Yang, Z., Wang, Y., Jiang, L., Zhou, N., Wang, X., Liu, B., Ma, Z., Wang, K., Li, H., Zhang, S., Shang, Y., & Yang, M. (2025). Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT). Proceedings of the National Academy of Sciences, 122(36). Martinez, E. J., Wong, D. H., Patel, A. J., Vaz, R. J., Busby, R. W., Zahler, R., Schefer, D., Zhao, H., Xu, X., Liu, Z., Meng, R., Kaiser, B., Liu, J., Wen, L., Liu, R., Leites, K., Tian, H. S., Tavazoie, S. F., Tavazoie, M. F., & Kurth, I. (2026). Carboxylic acid bioisosteres of creatine as novel and selective substrate competitive inhibitors of the creatine transporter SLC6A8. Journal of Medicinal Chemistry, 69(4), 3915-3931. Alhomsi, D., Abdalsalam, D., Sulaiman, R., Bakleh, S., & Alasmar, D. (2023). Novel guanidinoacetate methyltransferase (GAMT) mutation associated with cerebral creatine deficiency syndrome in a Syrian child: A case report. Annals of Medicine & Surgery, 85(5), 1906-1910. Almaghrabi, M. A., Muthaffar, O. Y., Alahmadi, S. A., Abdulsbhan, M. A., Bamusa, M., Aljezani, M. A., Bahowarth, S. Y., Alyazidi, A. S., & Aggad, W. S. (2023). GAMT deficiency among pediatric population: Clinical and molecular characteristics and management. Child Neurology Open, 10. Portales-Castillo, I., Singal, R., Ambrose, A., Song, J. H., Son, M., Goo, Y. A., Zhou, W., Traum, A. Z., Coler-Reilly, A., Humphreys, B. D., Civitelli, R., Jüppner, H., Lundquist, A. L., Seres, P., Allegretti, A. S., & Mercimek-Andrews, S. (2024). Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L GATM variant and study of organoids towards treatment. JIMD Reports, 65(5), 341-353. Alyazidi, A. S., Muthaffar, O. Y., Shawli, M. K., Ahmed, R. A., Aljefri, Y. F., Baaishrah, L. S., Jambi, A. T., & Alotibi, F. A. (2024). Phenotypic and molecular spectrum of guanidinoacetate N-methyltransferase deficiency: An analytical study of a case series and a scoping review of 53 cases of guanidinoacetate N-methyltransferase. Journal of Microscopy and Ultrastructure, 12(2), 81-90. Biagiotti, S., Perla, E., Guzzo, S. M., Tolve, M., Nardecchia, F., Rossi, L., Carducci, C., Pascucci, T., Leuzzi, V., & Magnani, M. (2025). GAMT deficiency: Clinical presentation, treatment, diagnosis, animal models, preclinical and clinical developments. International Journal of Molecular Sciences, 26(23), 11282. Ferretti, A., Battini, R., Gagliardo, O., Verrigni, D., Manca, M. B., Ferrari, A. R., Salerno, G., Boccia, R., Polese, D., Cocco, C., Zampogna, S., Di Nardo, G., Evangelisti, M., Pagani, J., Bruni, O., Romano, A., Piastra, M., Simmaco, M., Rocco, M., … Parisi, P. (2025). Epilepsy expands the phenotype of L-arginine:glycine amidinotransferase deficiency. Epilepsia, 66(11), 4425-4433. Oliva, C., Arias, A., Ruiz-Sala, P., Garcia-Villoria, J., Carling, R., Bierau, J., Ruijter, G. J. G., Casado, M., Ormazabal, A., & Artuch, R. (2024). Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: Validation through ERNDIM external quality assessment schemes. Clinical Chemistry and Laboratory Medicine, 62(10), 1991-2000. Kaufman, C., D’Andrea, A., Hackenberg, A., Poms, M., Braissant, O., & Häberle, J. (2025). Diagnostic delay in cerebral creatine deficiency disorders: Lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023. Molecular and Cellular Pediatrics, 12(1). Rahhal, S., Farmer, C., Thurm, A., Wassif, C. A., Cawley, N. X., Perreault, J., Dang Do, A., Bianconi, S., Hannah-Shmouni, F., Guthrie, W., Cubit, L. S., Miller, J. S., Sutton, V. R., Koeberl, D., & Porter, F. D. (2023). Elevated amyloid beta peptides and total tau in cerebrospinal fluid in individuals with creatine transporter deficiency. Molecular Genetics and Metabolism Reports, 37, 101001. Sugimoto, C., Perna, M. K., Regan, S. L., Tepe, E. A., Liou, R., Fritz, A. L., Williams, M. T., Vorhees, C. V., & Skelton, M. R. (2024). A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8 mice. Brain Research, 1825, 148690. Day, I., Tamboline, M., Lueptow, L., Zhuravka, I., Diep, T., Tkachyova, I., Xu, S., Schulze, A., & Lipshutz, G. S. (2025). [18F]FDG-PET and [18F]MPPF-PET are brain biomarkers for the creatine transporter Slc6a8 loss of function mutation. Scientific Reports, 15(1). Do, M.-H. T., Cavagnaro, J., Butt, M., Terse, P. S., & McKew, J. C. (2021). Use of an animal model of disease for toxicology enables identification of a juvenile no observed adverse effect level for cyclocreatine in creatine transporter deficiency. Regulatory Toxicology and Pharmacology, 123, 104939. Jomura, R., Akanuma, S.-I., Kubo, Y., Tachikawa, M., & Hosoya, K.-I. (2022). Processing mechanism of guanidinoacetate in choroid plexus epithelial cells: Conversion of guanidinoacetate to creatine via guanidinoacetate N-methyltransferase and monocarboxylate transporter 12-mediated creatine release into the CSF. Fluids and Barriers of the CNS, 19(1). Jomura, R., Sawada, M., Tega, Y., Akanuma, S.-I., Tachikawa, M., & Hosoya, K.-I. (2024). Molecular mechanism of SLC6A8 dysfunction with c.1699T > C (p.S567P) mutation in cerebral creatine deficiency syndromes. Biological and Pharmaceutical Bulletin, 47(1), 187-191. Diep, T., & Lipshutz, G. S. (2025). Evaluation of SLC6A8 species conservation and the effect of pathogenic variants on creatine transport. Human Genetics and Genomics Advances, 6(4), 100489. Miller, J. S., Farmer, C., Blair, S., Bianconi, S., Akshoomoff, N., Anselm, I., Barshop, B. A., Becker, L., Bennett, A. E., Berry, L. N., Berry-Kravis, E. M., Bruchey, A., Byars, A. W., Cimms, T., Cecil, K. M., Covello, M., Cubit, L. S., Das, T., Davis, R. J., … Thurm, A. (2026). Longitudinal characterization of males with X-linked creatine transporter deficiency: Final results of a multiyear observational study. Pediatric Neurology, 175, 8-18. Mustafa, N. M., Elabd, N. E., Selim, L. A., Abdou, D. M., & Griffin, J. L. (2022). Creatine deficiency syndromes: Comparison of screening methods and characterization of four novel intronic variants. Clinica Chimica Acta, 536, 70-76. Meera, P., Uusi-Oukari, M., Wallner, M., & Lipshutz, G. S. (2025). Guanidino compounds with native GABA(A) δ receptor selectivity: A tale of homeostatic compensation in δ-KO mice. BMC Neuroscience, 27(1). Ito, S., Uemura, T., Miyano, A., Shimbo, H., Masuda, T., Goto, T., Osaka, H., Wada, T., & Ohtsuki, S. (2025). Effects of SLC6A8 mutation-induced creatine deficiency on cellular function in fibroblasts. Scientific Reports, 15(1). Longo, N., Voss, L. A., Frigeni, M., Balakrishnan, B., & Pasquali, M. (2024). Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8. Molecular Genetics and Metabolism, 143(3), 108595. Tkachyova, I., Tropak, M. B., Lee, A., Datti, A., Ito, S., & Schulze, A. (2024). Targeting AGAT gene expression – a drug screening approach for the treatment of GAMT deficiency. Expert Opinion on Drug Discovery, 19(11), 1383-1397. Mabondzo, A., van de Kamp, J., & Mercimek-Andrews, S. (2024). Dodecyl creatine ester therapy: From promise to reality. Cellular and Molecular Life Sciences, 81(1). Borrell-Pichot, M., Fons, C., Boronat, S., & Sierra-Marcos, A. (2025). Successful management of refractory epilepsy in creatine transporter deficiency with cannabidiol and clobazam: A case report. Epilepsia Open, 10(1), 342-347. Nasseri Moghaddam, Z., Reinhardt, E. K., Thurm, A., Potter, B. K., Smith, M., Graham, C., Tiller, B. H., Baker, S. A., Bilder, D. A., Bogar, R., Britz, J., Cafferty, R., Coller, D. P., DeGrauw, T. J., Hall, V., Lipshutz, G. S., Longo, N., Mercimek-Andrews, S., Miller, J. S., … Wallis, H. (2025). Establishing a core outcome set for creatine transporter deficiency and guanidinoacetate methyltransferase deficiency. Orphanet Journal of Rare Diseases, 20(1). Caspi, L., Hayeems, R., & Schulze, A. (2025). Outcomes in early-treated guanidinoacetate methyltransferase deficiency: A sibling cohort study. Neurology Genetics, 11(3). Montani, C., Iovino, L., Di Vetta, F., Pasquin Mariani, J.-C. R., De Guzman, A. E., Gini, S., Galbusera, A., D’Epifanio, B., Ghirardini, E., Cornuti, S., Dadà, L., Putignano, E., Alessandrì, M. G., Vasirani, G., Bertozzi, S. M., Armirotti, A., Baroncelli, L., & Gozzi, A. (2026). Connectomic and behavioural alterations in creatine transporter deficiency are partially normalized by gene therapy. Brain, 149(3), 1043-1057. Benech, H., Flament, V., Lhotellier, C., Roucairol, C., & Joudinaud, T. (2026). New insights into drug development via the nose-to-brain pathway: Exemplification through dodecyl creatine ester for neuronal disorders. Pharmaceutics, 18(1), 80. Miller, D. W., & Hatch, G. M. (2023). Reduction in cardiolipin reduces expression of creatine transporter-1 and creatine transport in growing hCMEC/D3 human brain microvessel endothelial cells. Frontiers in Drug Delivery, 3. Tachikawa, M. (2026). Transporters for creatine and related guanidino compounds: Their relevance to brain health and disorders. Biological and Pharmaceutical Bulletin, 49(4), 601-617. Eda, I. R., Ramachandran, R., Joseph, V. M., Marreddy, S., & Mounika, A. (2025). Imaging the future: Diagnosing treatable neurometabolic disorders in children. Cureus. Stöckler-Ipsiroglu, S., Mercimek-Andrews, S., & Salomons, G. S. (2022). Disorders of creatine metabolism. In Inborn Metabolic Diseases (pp. 239-245). Springer Berlin Heidelberg. Lyons, E. L., Watson, D., Alodadi, M. S., Haugabook, S. J., Tawa, G. J., Hannah-Shmouni, F., Porter, F. D., Collins, J. R., Ottinger, E. A., & Mudunuri, U. S. (2023). Rare disease variant curation from literature: Assessing gaps with creatine transport deficiency in focus. BMC Genomics, 24(1). Afjei, S. A., Mohammadi, M. F., Pourbakhtyaran, E., Ghabeli, H., Ashrafi, M. R., Haghighi, R., Rasulinezhad, M., Pak, N., Tavasoli, A. R., & Heidari, M. (2023). Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT. neurogenetics, 24(2), 67-78. Balestrino, M., Adriano, E., Alì, P. A., & Pardini, M. (2024). Selective alteration of the left arcuate fasciculus in two patients affected by creatine transporter deficiency. Brain Sciences, 14(4), 337. Silverman, A., Africk, B., & Duane, D. (2025). Child Neurology: Creatine biosynthesis disorder in an adolescent with Capgras syndrome and reduplicative paramnesia. Neurology, 104(9). Schifino, M., Bartolini, E., Pagano, S., Meossi, C., Pasquariello, R., & Battini, R. (2025). Dynamic electro-clinical features in guanidinoacetate N-methyltransferase deficiency: A familial case series. Epilepsia Open, 10(4), 1244-1252. Delinière, A., Mulatier, C., Cheillan, D., Gheurbi, F., Buchy, M., Dufay, N., Moulin-Zinsch, A., Bertail-Galoin, C., Sabour, M., Aarab, M., Perouse de Montclos, T., Ouvrier-Buffet, D., Boisson, A., Stos, B., Rharbaoui, M., Remerand, G., Barnerias, C., Brassier, A., Goldenberg, A., … Curie, A. (2026). Prominent U-waves without QT prolongation in X-linked creatine transporter deficiency caused by SLC6A8 variants. Heart Rhythm, 23(3), 700-709. Sanders, K., Peck, D., Bentz Pino, G., Studinski Jones, A., White, A., Gavrilov, D., Matern, D., Oglesbee, D., Schultz, M., Tortorelli, S., & Hall, P. L. (2024). SLC6A8 creatine transporter deficiency can be detected by plasma creatine and creatinine concentrations. Molecular Genetics and Metabolism, 142(1), 108455. Lee, A., Anderson, L., Tkachyova, I., Tropak, M. B., Wang, D., & Schulze, A. (2024). Validation and optimization of a stable isotope-labeled substrate assay for measuring AGAT activity. International Journal of Molecular Sciences, 25(23), 12490. Poggio, F., Brofiga, M., Tedesco, M., Massobrio, P., Adriano, E., & Balestrino, M. (2022). Lack of epileptogenic effects of the creatine precursor guanidinoacetic acid on neuronal cultures in vitro. Biomolecules, 13(1), 74. Yang, J., Palsule, G., Jiao, X., Messenger, J. S., Hart, R. P., & Kiledjian, M. (2025). Creatine mitigates neurogenesis impairment caused by defective DcpS decapping. Scientific Reports, 15(1). Abdullah, K. G., Miki, K., Edgar, C. K., Wu, S. A., Xiao, Y., Huang, Y.-T., Drexler, R., Krishna, S., Puliyappadamba, V. T., Tay, L. W. R., Yuan, F., Savani, M. R., Ghoche, M. T., Kotermanski, S. E., Traylor, J. I., Guo, L., Gunn, K., Hicks, W. H., Shi, D. D., … McBrayer, S. K. (2026). Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth. Cell. Lee, A., Weisenberg, J., Toolan, E., & Shinawi, M. (2025). Treatment and improved outcomes of three adult patients with guanidinoacetate methyltransferase (GAMT) deficiency. JIMD Reports, 66(3). Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F., & Caron, M. G. (1994). Cloning, pharmacological characterization, and genomic localization of the human creatine transporter. Receptors & Channels, 2(2), 165–174. Stary, D., El-Kasaby, A., Boytsov, D., Zaręba, P., Godyń, J., Maszczyk, M., Rzepka, Z., Wrześniok, D., Sotriffer, C., Sandtner, W., Freissmuth, M., & Bajda, M. (2026). Structure-based search for novel creatine transporter inhibitors. ACS Medicinal Chemistry Letters, 17(6), 1355-1363. Poudel, P., Panday, S. K., & Alexov, E. (2026). From extracellular entry to intracellular release: A water-assisted transport cycle for creatine in SLC6A8. Protein Science, 35(7). Gadian, D. G. (1982). Nuclear magnetic resonance and its applications to living systems. Clarendon Press; Oxford University Press. de Graaf, R. A. (1998). In vivo NMR spectroscopy: Principles and techniques. John Wiley & Sons. Sharma, S., Yadav, T., Saini, L., & Tiwari, S. (2026). Creatine deficiency syndrome: Significance of magnetic resonance spectroscopy. Indian Journal of Pediatrics, 93(4), 409-410. Cecil, K. M., Henry, P. G., Wallis, H., Thurm, A., & Roberts, T. P. L. (2026). A call for pediatric magnetic resonance spectroscopy harmonization in neurometabolic disorders with a simple approach for diagnosis, treatment monitoring and data aggregation for clinical trials. American Journal of Neuroradiology. Wang, Z., Zhang, H., Wang, J., Zhang, Y., & Huang, J. (2026). Comparing multi-pool Lorentzian fitting methods for guanidinium CEST quantification in the human brain at clinical 3 T : A validation study using MRS. Magnetic Resonance in Medicine. Stöckler, S., Isbrandt, D., Hanefeld, F., Schmidt, B., & von Figura, K. (1996). Guanidinoacetate methyltransferase deficiency: The first inborn error of creatine metabolism in man. American Journal of Human Genetics, 58(5), 914–922. Yang, L., Fang, F., Jin, H., & Wu, Y. (2024). [Clinical characterisation of creatine transporter deficiency associated with SLC6A8 gene variants]. Zhonghua Er Ke Za Zhi (Chinese Journal of Pediatrics), 62(12), 1202–1207. https://doi.org/10.3760/cma.j.cn112140-20240715-00485 Chehowah, C., Mittelman, A., & des Portes, V. (2025). An international questionnaire highlights and supports the case for including girls in creatine transporter deficiency research. Frontiers in Neuroscience, 19. Huang, J., Digles, D., & Ecker, G. F. (2025). Mutation hot spots for clinical pathogenicity across the SLC6 transporter family. bioRxiv. Wallis, H., Iyer, S., & Reinhardt, E. K. (2025). How a patient-led advocacy organization supports the road to diagnosis and treatment of creatine transporter deficiency. Frontiers in Neuroscience, 19. Zhao, T. T., Pan, Z., Zhong, J. M., Tang, H. Y., Yin, F., Peng, J., & Chen, C. (2025). [Two cases of creatine deficiency syndrome caused by GAMT gene mutations and literature review]. Zhongguo Dang Dai Er Ke Za Zhi (Chinese Journal of Contemporary Pediatrics), 27(3), 340–346. https://doi.org/10.7499/j.issn.1008-8830.2411062 Mercimek-Andrews, S., & Salomons, G. S. (2025). Creatine deficiency disorders. In M. P. Adam, S. Bick, G. M. Mirzaa, S. E. Wallace, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK3794/ (Original work published 2009) Alessandrì, M. G., Bosetti, C., Scaffei, E., Casalini, C., Balestrini, S., Tramacere, L., Ambrosi, P., Tosetti, M., Guerrini, R., & Battini, R. (2026). Advancing clinical insight into creatine transporter deficiency: Long term outcome and new observations from the Italian cohort. Orphanet Journal of Rare Diseases, 21(1). Burgac, E., Çelik, M. Y., Bulut, F. D., Kaplan, İ., Köseci, B., Kara, E., Gündüz, N. T., Mert, G. G., Kaya, Ö., Kor, D., & Mungan, N. Ö. (2026). Creatine deficiency syndromes: Clinical spectrum, neuroimaging features and treatment response. International Journal of Developmental Neuroscience, 86(5). Kilic, M. A., Karaman, V., Gencpinar, P., Sakarya Gunes, A., Sonmez, F. M., Aydin, H. I., Bildik, O., Sager, S. G., Aksu Uzunhan, T., Gunay, C., Ates Yaman, O., Ercelebi, H., Basarir, G., Gok, A., Ersoy, M., Sunnetci Akkoyunlu, D., Polat, H., Turkyilmaz, A., Turan, B., … Maras Genc, H. (2026). Diagnostic timing in cerebral creatine deficiency syndromes: Neurodevelopmental and genetic characterization of a multicenter cohort. European Journal of Pediatrics, 185(11). Perreault, J., Porter, F. D., & Nowaczyk, M. J. M. (2026). Delineation of facial dysmorphology in males with creatine transporter defect. American Journal of Medical Genetics Part A, 200(7), 1740-1741. Leonardi, H., Minor, K. M., Fritz, J., Friedenberg, S. G., Cullen, J. N., Guo, L. T., & Shelton, G. D. (2026). Myopathy due to a creatine deficiency disorder in a family of mixed breed dogs with a glycine amidinotransferase gene mutation. Journal of Veterinary Internal Medicine, 40(1). Smith, D. E. C., Wamelink, M. M. C., Salomons, G. S., & van de Kamp, J. M. (2024). Creatine and its metabolites. In Laboratory Guide to the Methods in Biochemical Genetics (pp. 475-485). Springer International Publishing. Meiouet, F., & Boemer, F. (2026). Rapid LC-MS/MS method for targeted assay of creatine deficiency syndromes in Morocco. Metabolites, 16(6), 388. Pan, X., & Sun, Q. (2027). Cerebral creatine deficiency syndromes. In Laboratory Diagnosis of Inherited Metabolic Diseases (pp. 363-375). Elsevier. Skelton, M. R., Liou, R., & Perna, M. K. (2022). Creatine transporter (Slc6a8) knockout mice show an inattentive-like phenotype in the 5-choice serial reaction time test. bioRxiv. Duran-Trio, L., Lanzillo, M., Simicic, D., Roux-Petronelli, C., Bruce, S. J., Sandi, C., Cudalbu, C., & Braissant, O. (2025). Heterozygous females from a rat model for creatine transporter deficiency reveal altered behavioral response to stressors, normal body weight and slight metabolic changes. Frontiers in Neuroscience, 19. Branovets, J., Laasmaa, M., Stolova, J., Shen, X., Rätsepso, T., Bernasconi, R., Soodla, K., Balodis, M. J., Grahv, C., Hendrikson, E., Louch, W. E., Birkedal, R., & Vendelin, M. (2025). Lifelong creatine deficiency leads to augmented sarcoplasmic reticulum calcium release but not heart failure. American Journal of Physiology-Heart and Circulatory Physiology, 329(2), H471-H489. Ito, S., Iwata, Y., Uemura, T., Sugimoto, M., Kumabe, H., Miyano, A., Nakamura, T., Tashiro, N., Ieiri, M., Umezaki, M., Chikamatsu, S., Masuda, T., Nakao, S., Nakagata, N., Takeo, T., Araki, K., & Ohtsuki, S. (2026). Stage- and region-dependent proteomic alterations in a mouse model of creatine transporter deficiency. Journal of Neuroscience, 46(30), e2010252026. Perna, M. K., Gechijian, L. N., Blanchette, H. S., Liou, R., Williams, M. T., Vorhees, C. V., & Skelton, M. R. (2026). A mouse model of a patient derived P544L mutation in the Slc6a8 gene shows hypoactivity and cognitive deficits. Brain Research, 1874, 150151. Bianchi, M. C., Tosetti, M., Battini, R., Leuzzi, V., Alessandri', M. G., Carducci, C., Antonozzi, I., & Cioni, G. (2007). Treatment monitoring of brain creatine deficiency syndromes: A 1H- and 31P-MR spectroscopy study. American Journal of Neuroradiology, 28(3), 548–554. Tkachyova, I., Wang, D., Lee, A., Rößler, P., Atienza, J., Feugmann, J., Guischard, N., Hui, A., Shi, C., & Schulze, A. (2026). Creatine supplementation reduces guanidinoacetate via downregulation of AGAT in a mouse model of GAMT deficiency. Journal of Inherited Metabolic Disease, 49(5). Binsfeld, R., Webster, T., Tkachyova, I., Tropak, M., Mitchell, M., Peretti, T., Schulze, A., & Walia, J. S. (2026). A CNS-directed, AAV9 gene therapy restores expression and biochemical function of guanidinoacetate methyltransferase in models of GAMT deficiency. International Journal of Molecular Sciences, 27(2), 1035. Sung, W., Chen, H., Hsu, C., & Tsai, M. (2026). Reversal of refractory epilepsy in an adult with GAMT deficiency: A case report and comparative literature review. Epilepsia Open. Wang, K., Liu, C., He, J., Xu, M., Li, L., & Li, H. (2026). Targeting the creatine transporter SLC6A8: Mechanisms and emerging therapeutic strategies for multiple diseases. Biochemical Pharmacology, 251, 118167. Jaffe, M. (1886). Ueber den Niederschlag, welchen Pikrinsäure in normalem Harn erzeugt und über eine neue Reaction des Kreatinins. bchm, 10(5), 391-400. Jaffe 1886 Bonsnes, R. W., & Taussky, H. H. (1945). On the colorimetric determination of creatinine by the Jaffe reaction. Journal of Biological Chemistry, 158(3), 581-591. Bonsnes 1945 Walker, J. B. (1979). Creatine: Biosynthesis, regulation, and function. Advances in Enzymology - and Related Areas of Molecular Biology. Walker 1979 De Deyn, P. P., & Macdonald, R. L. (1990). Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture. Annals of Neurology, 28(5), 627-633. De Deyn 1990 Wallimann, T., Wyss, M., Brdiczka, D., Nicolay, K., & Eppenberger, H. M. (1992). Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: The ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochemical Journal, 281(1), 21-40. Wallimann 1992 Guimbal, C., & Kilimann, M. W. (1993). A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. Journal of Biological Chemistry, 268(12), 8418-8421. Guimbal 1993 Provencher, S. W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 30(6), 672-679. Provencher 1993 Stöckler, S., Holzbach, U., Hanefeld, F., Marquardt, I., Helms, G., Requart, M., Hänicke, W., & Frahm, J. (1994). Creatine deficiency in the brain: A New, treatable inborn error of metabolism. Pediatric Research, 36(3), 409-413. Stöckler 1994 Stöckler, S., Hanefeld, F., & Frahm, J. (1996). Creatine replacement therapy in guanidineoacetate methyltransferase deficiency, a novel inborn error of metabolism. The Lancet, 348(9030), 789-790. Stöckler 1996 Vanhamme, L., van den Boogaart, A., & Van Huffel, S. (1997). Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. Journal of Magnetic Resonance, 129(1), 35-43. Vanhamme 1997 Schulze, A., Hess, T., Wevers, R., Mayatepek, E., Bachert, P., Marescau, B., Knopp, M. V., De Deyn, P. P., Bremer, H. J., & Rating, D. (1997). Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: Diagnostic tools for a new inborn error of metabolism. The Journal of Pediatrics, 131(4), 626-631. Schulze 1997 Laughlin, S. B., de Ruyter van Steveninck, R. R., & Anderson, J. C. (1998). The metabolic cost of neural information. Nature Neuroscience, 1(1), 36-41. Laughlin 1998 Struys, E. A., Jansen, E. E. W., ten Brink, H. J., Verhoeven, N. M., van der Knaap, M. S., & Jakobs, C. (1998). An accurate stable isotope dilution gas chromatographic–mass spectrometric approach to the diagnosis of guanidinoacetate methyltransferase deficiency. Journal of Pharmaceutical and Biomedical Analysis, 18(4-5), 659-665. Struys 1998 Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological Reviews, 80(3), 1107-1213. Wyss 2000 Govindaraju, V., Young, K., & Maudsley, A. A. (2000). Proton NMR chemical shifts and coupling constants for brain metabolites. NMR in Biomedicine, 13(3), 129-153. Govindaraju 2000 Bianchi, M. C., Tosetti, M., Fornai, F., Alessandri, M. G., Cipriani, P., De Vito, G., & Canapicchi, R. (2000). Reversible brain creatine deficiency in two sisters with normal blood creatine level. Annals of Neurology, 47(4), 511-513. Bianchi 2000 Braissant, O., Henry, H., Loup, M., Eilers, B., & Bachmann, C. (2001). Endogenous synthesis and transport of creatine in the rat brain: An in situ hybridization study. Molecular Brain Research, 86(1-2), 193-201. Braissant 2001 Provencher, S. W. (2001). Automatic quantitation of localized in vivo1H spectra with LCModel. NMR in Biomedicine, 14(4), 260-264. Provencher 2001 Attwell, D., & Laughlin, S. B. (2001). An energy budget for signaling in the grey matter of the brain. Journal of Cerebral Blood Flow & Metabolism, 21(10), 1133-1145. Attwell 2001 Cecil, K. M., Salomons, G. S., Ball, W. S., Wong, B., Chuck, G., Verhoeven, N. M., Jakobs, C., & DeGrauw, T. J. (2001). Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect? Annals of Neurology, 49(3), 401-404. Cecil 2001 Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J., & Jakobs, C. (2001). X-linked creatine-transporter gene (SLC6A8) defect: A New creatine-deficiency syndrome. The American Journal of Human Genetics, 68(6), 1497-1500. Salomons 2001 Item, C. B., Stöckler-Ipsiroglu, S., Stromberger, C., Mühl, A., Alessandrì, M. G., Bianchi, M. C., Tosetti, M., Fornai, F., & Cioni, G. (2001). Arginine:Glycine amidinotransferase deficiency: The third inborn error of creatine metabolism in humans. The American Journal of Human Genetics, 69(5), 1127-1133. Item 2001 Schulze, A., Ebinger, F., Rating, D., & Mayatepek, E. (2001). Improving treatment of guanidinoacetate methyltransferase deficiency: Reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. Molecular Genetics and Metabolism, 74(4), 413-419. Schulze 2001 Ohtsuki, S., Tachikawa, M., Takanaga, H., Shimizu, H., Watanabe, M., Hosoya, K.-I., & Terasaki, T. (2002). The blood–brain barrier creatine transporter is a major pathway for supplying creatine to the brain. Journal of Cerebral Blood Flow & Metabolism, 22(11), 1327-1335. Ohtsuki 2002 Neu, A., Neuhoff, H., Trube, G., Fehr, S., Ullrich, K., Roeper, J., & Isbrandt, D. (2002). Activation of GABAA receptors by guanidinoacetate: A novel pathophysiological mechanism. Neurobiology of Disease, 11(2), 298-307. Neu 2002 Shevell, M., Ashwal, S., Donley, D., Flint, J., Gingold, M., Hirtz, D., Majnemer, A., Noetzel, M., & Sheth, R. D. (2003). Practice parameter: Evaluation of the child with global developmental delay [RETIRED]: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology, 60(3), 367-380. Shevell 2003 Schulze, A. (2003). Creatine deficiency syndromes. Molecular and Cellular Biochemistry, 244(1-2), 143-150. Schulze 2003 Salomons, G. S., Van Dooren, S. J. M., Verhoeven, N. M., Marsden, D., Schwartz, C., Cecil, K. M., DeGrauw, T. J., & Jakobs, C. (2003). X-linked creatine transporter defect: An overview. Journal of Inherited Metabolic Disease, 26(2-3), 309-318. Salomons 2003 deGrauw, T. J., Cecil, K. M., Byars, A. W., Salomons, G. S., Ball, W. S., & Jakobs, C. (2003). The clinical syndrome of creatine transporter deficiency. Molecular and Cellular Biochemistry, 244(1-2), 45-48. deGrauw 2003 Schulze, A., Bachert, P., Schlemmer, H., Harting, I., Polster, T., Salomons, G. S., Verhoeven, N. M., Jakobs, C., Fowler, B., Hoffmann, G. F., & Mayatepek, E. (2003). Lack of creatine in muscle and brain in an adult with GAMT deficiency. Annals of Neurology, 53(2), 248-251. Schulze 2003 Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., & Salomons, G. S. (2004). High prevalence of SLC6A8 deficiency in X-linked mental retardation. The American Journal of Human Genetics, 75(1), 97-105. Rosenberg 2004 Almeida, L. S., Verhoeven, N. M., Roos, B., Valongo, C., Cardoso, M. L., Vilarinho, L., Salomons, G. S., & Jakobs, C. (2004). Creatine and guanidinoacetate: Diagnostic markers for inborn errors in creatine biosynthesis and transport. Molecular Genetics and Metabolism, 82(3), 214-219. Almeida 2004 Schmidt, A. (2004). Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency. Human Molecular Genetics, 13(9), 905-921. Schmidt 2004 Almeida, L. S., Salomons, G. S., Hogenboom, F., Jakobs, C., & Schoffelmeer, A. N. M. (2006). Exocytotic release of creatine in rat brain. Synapse, 60(2), 118-123. Almeida 2006 Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., & Salomons, G. S. (2006). X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Human Genetics, 119(6), 604-610. Clark 2006 Lion-François, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gérard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., & des Portes, V. (2006). High frequency of creatine deficiency syndromes in patients with unexplained mental retardation. Neurology, 67(9), 1713-1714. Lion-François 2006 Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araújo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Mühl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., … Jakobs, C. (2006). GAMT deficiency: Features, treatment, and outcome in an inborn error of creatine synthesis. Neurology, 67(3), 480-484. Mercimek-Mahmutoglu 2006 Schulze, A., Hoffmann, G. F., Bachert, P., Kirsch, S., Salomons, G. S., Verhoeven, N. M., & Mayatepek, E. (2006). Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology, 67(4), 719-721. Schulze 2006 Battini, R., Alessandrì, M. G., Leuzzi, V., Moro, F., Tosetti, M., Bianchi, M. C., & Cioni, G. (2006). Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: Early treatment can prevent phenotypic expression of the disease. The Journal of Pediatrics, 148(6), 828-830. Battini 2006 Brosnan, J. T., & Brosnan, M. E. (2007). Creatine: Endogenous metabolite, dietary, and therapeutic supplement. Annual Review of Nutrition, 27(1), 241-261. Brosnan 2007 Braissant, O., Béard, E., Torrent, C., & Henry, H. (2010). Dissociation of AGAT, GAMT and SLC6A8 in CNS: Relevance to creatine deficiency syndromes. Neurobiology of Disease, 37(2), 423-433. Braissant 2010 Skelton, M. R., Schaefer, T. L., Graham, D. L., deGrauw, T. J., Clark, J. F., Williams, M. T., & Vorhees, C. V. (2011). Creatine transporter (CrT; Slc6a8) knockout mice as a model of human CrT deficiency. PLoS ONE, 6(1), e16187. Skelton 2011 Harris, J. J., Jolivet, R., & Attwell, D. (2012). Synaptic energy use and supply. Neuron, 75(5), 762-777. Harris 2012 Kurosawa, Y., DeGrauw, T. J., Lindquist, D. M., Blanco, V. M., Pyne-Geithman, G. J., Daikoku, T., Chambers, J. B., Benoit, S. C., & Clark, J. F. (2012). Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency. Journal of Clinical Investigation, 122(8), 2837-2846. Kurosawa 2012 van de Kamp, J. M., Betsalel, O. T., Mercimek-Mahmutoglu, S., Abulhoul, L., Grünewald, S., Anselm, I., Azzouz, H., Bratkovic, D., de Brouwer, A., Hamel, B., Kleefstra, T., Yntema, H., Campistol, J., Vilaseca, M. A., Cheillan, D., D’Hooghe, M., Diogo, L., Garcia, P., Valongo, C., … Salomons, G. S. (2013). Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. Journal of Medical Genetics, 50(7), 463-472. van de Kamp 2013 Moeschler, J. B., Shevell, M., Moeschler, J. B., Shevell, M., Saul, R. A., Chen, E., Freedenberg, D. L., Hamid, R., Jones, M. C., Stoler, J. M., & Tarini, B. A. (2014). Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics, 134(3), e903-e918. Moeschler 2014 van de Kamp, J. M., Mancini, G. M., & Salomons, G. S. (2014). X-linked creatine transporter deficiency: Clinical aspects and pathophysiology. Journal of Inherited Metabolic Disease, 37(5), 715-733. van de Kamp 2014 Stockler-Ipsiroglu, S., van Karnebeek, C., Longo, N., Korenke, G. C., Mercimek-Mahmutoglu, S., Marquart, I., Barshop, B., Grolik, C., Schlune, A., Angle, B., Araújo, H. C., Coskun, T., Diogo, L., Geraghty, M., Haliloglu, G., Konstantopoulou, V., Leuzzi, V., Levtova, A., MacKenzie, J., … Schulze, A. (2014). Guanidinoacetate methyltransferase (GAMT) deficiency: Outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Molecular Genetics and Metabolism, 111(1), 16-25. Stockler-Ipsiroglu 2014