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Pathway Description
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-11-03
Guanidinoacetate Methyltransferase Deficiency (Creatine-Deficiency-Syndrome) is a rare autosomal recessive disease caused by a mutation in the GAMT gene which codes for guanidinoacetate N-methyltransferase. A deficiency in this enzyme results in accumulation of 3-methylglutaconic acid in urine; guanidoacetic acid in urine and serum. Decreased concentrations of creatine are found in serum and urine; and creatinine in plasma, spinal fluid, and urine. Symptoms, which present at birth, include failure to thrive, mental and motor retardation, hyoptonia, and seizures. Treatment includes arginine-restricted diet, sodium benzoate, and L-ornithine hydrochlorate.
References
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency) References
[OMIM: Entry 612736](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=612736)
[Uniprot: Q14353](http://www.uniprot.org/uniprot/Q14353)
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Pubmed: 15651030
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Pubmed: 19289269
Arginine and Proline Metabolism References
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Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 19030957
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Pubmed: 9806879
Bock HG, Su TS, O'Brien WE, Beaudet AL: Sequence for human argininosuccinate synthetase cDNA. Nucleic Acids Res. 1983 Sep 24;11(18):6505-12. doi: 10.1093/nar/11.18.6505.
Pubmed: 6194510
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O'Brien WE, McInnes R, Kalumuck K, Adcock M: Cloning and sequence analysis of cDNA for human argininosuccinate lyase. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7211-5. doi: 10.1073/pnas.83.19.7211.
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Finckh U, Kohlschutter A, Schafer H, Sperhake K, Colombo JP, Gal A: Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998;12(3):206-11. doi: 10.1002/(SICI)1098-1004(1998)12:3<206::AID-HUMU8>3.0.CO;2-E.
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Pubmed: 12955727
Aoshima T, Kajita M, Sekido Y, Kikuchi S, Yasuda I, Saheki T, Watanabe K, Shimokata K, Niwa T: Novel mutations (H337R and 238-362del) in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency. Hum Hered. 2001;52(2):99-101. doi: 10.1159/000053360.
Pubmed: 11474210
Nakatani Y, Banner C, von Herrath M, Schneider ME, Smith HH, Freese E: Comparison of human brain and liver glutamate dehydrogenase cDNAS. Biochem Biophys Res Commun. 1987 Dec 16;149(2):405-10. doi: 10.1016/0006-291x(87)90381-0.
Pubmed: 3426581
Amuro N, Yamaura M, Goto Y, Okazaki T: Molecular cloning and nucleotide sequence of the cDNA for human liver glutamate dehydrogenase precursor. Biochem Biophys Res Commun. 1988 May 16;152(3):1395-400. doi: 10.1016/s0006-291x(88)80440-6.
Pubmed: 3377777
Nakatani Y, Schneider M, Banner C, Freese E: Complete nucleotide sequence of human glutamate dehydrogenase cDNA. Nucleic Acids Res. 1988 Jul 11;16(13):6237. doi: 10.1093/nar/16.13.6237.
Pubmed: 3399399
Inana G, Totsuka S, Redmond M, Dougherty T, Nagle J, Shiono T, Ohura T, Kominami E, Katunuma N: Molecular cloning of human ornithine aminotransferase mRNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1203-7. doi: 10.1073/pnas.83.5.1203.
Pubmed: 3456579
Ramesh V, Shaffer MM, Allaire JM, Shih VE, Gusella JF: Investigation of gyrate atrophy using a cDNA clone for human ornithine aminotransferase. DNA. 1986 Dec;5(6):493-501.
Pubmed: 3816496
Kobayashi T, Nishii M, Takagi Y, Titani K, Matsuzawa T: Molecular cloning and nucleotide sequence analysis of mRNA for human kidney ornithine aminotransferase. An examination of ornithine aminotransferase isozymes between liver and kidney. FEBS Lett. 1989 Sep 25;255(2):300-4. doi: 10.1016/0014-5793(89)81110-x.
Pubmed: 2507357
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Pubmed: 8621661
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Pubmed: 14702039
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Pubmed: 16710414
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Pubmed: 15662599
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Pubmed: 11891283
Campbell HD, Webb GC, Young IG: A human homologue of the Drosophila melanogaster sluggish-A (proline oxidase) gene maps to 22q11.2, and is a candidate gene for type-I hyperprolinaemia. Hum Genet. 1997 Nov;101(1):69-74. doi: 10.1007/s004390050589.
Pubmed: 9385373
Nakayama T, Al-Maawali A, El-Quessny M, Rajab A, Khalil S, Stoler JM, Tan WH, Nasir R, Schmitz-Abe K, Hill RS, Partlow JN, Al-Saffar M, Servattalab S, LaCoursiere CM, Tambunan DE, Coulter ME, Elhosary PC, Gorski G, Barkovich AJ, Markianos K, Poduri A, Mochida GH: Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination. Am J Hum Genet. 2015 May 7;96(5):709-19. doi: 10.1016/j.ajhg.2015.03.003. Epub 2015 Apr 9.
Pubmed: 25865492
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