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Chapter 28 - Disorders of Creatine Metabolism: Creatine Deficiency Syndromes and Movement Disorders

from Section II - A Metabolism-Based Approach to Movement Disorders and Inherited Metabolic Disorders

Published online by Cambridge University Press:  24 September 2020

By
Saadet Mercimek-Andrews
Edited by
Darius Ebrahimi-Fakhari  and
Phillip L. Pearl
Darius Ebrahimi-Fakhari
Affiliation:
Harvard Medical School
Phillip L. Pearl
Affiliation:
Harvard Medical School
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Summary

Creatine is synthetized from two amino acids, arginine and glycine, in the kidney, liver, and pancreas. Two enzymes that are involved in the synthesis of creatine are L-arginine:glycine amidinotransferase (AGAT) (EC 2.1.4.1), highly expressed in the kidney, and guanidinoacetate N-methyltransferase (GAMT) (EC 2.1.1.2), which is highly expressed in the liver.

Type
Chapter
Information
Movement Disorders and Inherited Metabolic Disorders
Recognition, Understanding, Improving Outcomes
 , pp. 342 - 347
Publisher: Cambridge University Press
Print publication year: 2020

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References

Mercimek-Mahmutoglu, S, Salomons, GS. Creatine deficiency syndromes. GeneReviews®. 2009;Jan 15 (updated Dec 10, 2015).Google Scholar
Desroches, CL, Patel, J, Wang, P, et al. Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene. Mol Genet Genomics. 2015;290(6):2163–71.Google Scholar
DesRoches, CL, Bruun, T, Wang, P, Marshall, CR, Mercimek-Mahmutoglu, S. Arginine–glycine amidinotransferase deficiency and functional characterization of missense variants in GATM. Hum Mutat. 2016;37(9):926–32.CrossRefGoogle ScholarPubMed
DesRoches, CL, Patel, J, Wang, P, et al. 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. 2015;565(2):187–91.CrossRefGoogle ScholarPubMed
Stockler, S, Holzbach, U, Hanefeld, F, et al. Creatine deficiency in the brain: A new, treatable inborn error of metabolism. Pediatr Res. 1994;36(3):409–13.CrossRefGoogle Scholar
Mercimek-Mahmutoglu, S, Stoeckler-Ipsiroglu, S, Adami, A, et al. GAMT deficiency: Features, treatment, and outcome in an inborn error of creatine synthesis. Neurology. 2006;67(3):480–4.Google Scholar
Stockler-Ipsiroglu, S, van Karnebeek, C, Longo, N, et al. Guanidinoacetate methyltransferase (GAMT) deficiency: Outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Mol Genet Metab. 2014;111(1):16–25.CrossRefGoogle ScholarPubMed
Mercimek-Mahmutoglu, S, Ndika, J, Kanhai, W, et al. Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Hum Mutat. 2014;35(4):462–9.CrossRefGoogle ScholarPubMed
Khaikin, Y, Sidky, S, Abdenur, J, et al. Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. Eur J Paediatr Neurol. 2018;22(3):369–79.Google Scholar
O’Rourke, DJ, Ryan, S, Salomons, G, et al. Guanidinoacetate methyltransferase (GAMT) deficiency: Late onset of movement disorder and preserved expressive language. Dev Med Child Neurol. 2009;51(5):404–7.CrossRefGoogle ScholarPubMed
Dhar, SU, Scaglia, F, Li, FY, et al. Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab. 2009;96(1):38–43.CrossRefGoogle ScholarPubMed
Morris, AA, Appleton, RE, Power, B, et al. Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy. J Inherit Metab Dis. 2007;30(1):100.Google Scholar
Item, CB, Stockler-Ipsiroglu, S, Stromberger, C, et al. Arginine:glycineamidinotransferase deficiency: The third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001;69(5):1127–33.CrossRefGoogle Scholar
Stockler-Ipsiroglu, S, Apatean, D, Battini, R, et al. Arginine:glycineamidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide. Mol Genet Metab. 2015;116(4):252–9.Google Scholar
Salomons, GS, van Dooren, SJ, Verhoeven, NM, et al. X-linked creatine-transporter gene (SLC6A8) defect: A new creatine-deficiency syndrome. Am J Hum Genet. 2001;68(6):1497–500.CrossRefGoogle ScholarPubMed
van de Kamp, JM, Betsalel, OT, Mercimek-Mahmutoglu, S, et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013;50(7):463–72.CrossRefGoogle ScholarPubMed
van de Kamp, JM, Mancini, GM, Salomons, GS. X-linked creatine transporter deficiency: Clinical aspects and pathophysiology. J Inherit Metab Dis. 2014;37(5):715–33.Google Scholar
Anselm, IA, Alkuraya, FS, Salomons, GS, et al. X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype. J Inherit Metab Dis. 2006;29(1):214–9.Google Scholar
van Spronsen, FJ, Reijngoud, DJ, Verhoeven, NM, et al. High cerebral guanidinoacetate and variable creatine concentrations in argininosuccinate synthetase and lyase deficiency: Implications for treatment? Mol Genet Metab. 2006;89(3):274–6.Google Scholar
Nanto-Salonen, K, Komu, M, Lundbom, N, et al. Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia. Neurology. 1999;53(2):303–7.Google Scholar
Martinelli, D, Haberle, J, Rubio, V, et al. Understanding pyrroline-5-carboxylate synthetase deficiency: Clinical, molecular, functional, and expression studies, structure-based analysis, and novel therapy with arginine. J Inherit Metab Dis. 2012;35(5):761–76.Google Scholar
Schulze, A, Hoffmann, GF, Bachert, P, et al. Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology. 2006;67(4):719–21.CrossRefGoogle ScholarPubMed
El-Gharbawy, AH, Goldstein, JL, Millington, DS, et al. Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency. Mol Genet Metab. 2013;109(2):215–7.Google Scholar
Viau, KS, Ernst, SL, Pasquali, M, et al. Evidence-based treatment of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab. 2013;110(3):255–62.Google Scholar
Ndika, JD, Johnston, K, Barkovich, JA, et al. Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine: glycineamidinotransferase deficiency. Mol Genet Metab. 2012;106(1):48–54.CrossRefGoogle ScholarPubMed
Battini, R, Alessandri, MG, Leuzzi, V, et al. Arginine:glycineamidinotransferase (AGAT) deficiency in a newborn: Early treatment can prevent phenotypic expression of the disease. J Pediatr. 2006;148(6):828–30.Google Scholar
Valayannopoulos, V, Boddaert, N, Chabli, A, et al. Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect. J Inherit Metab Dis. 2012;35(1):151–7.CrossRefGoogle ScholarPubMed
van de Kamp, JM, Pouwels, PJ, Aarsen, FK, et al. Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect. J Inherit Metab Dis. 2012;35(1):141–9.Google Scholar
Chilosi, A, Leuzzi, V, Battini, R, et al. Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. Neurocase. 2008;14(2):151–61.Google Scholar
Fons, C, Sempere, A, Arias, A, et al. Arginine supplementation in four patients with X-linked creatine transporter defect. J Inherit Metab Dis. 2008;31(6):724–8.Google Scholar
Bruun, TUJ, Sidky, S, Bandeira, AO, et al. Treatment outcome of creatine transporter deficiency: International retrospective cohort study. Metab Brain Dis. 2018;33(3):875–84.Google Scholar

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