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Pathway Description
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-11-03
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency, Creatine Deficiency Syndrome, Creatine Deficiency due to AGAT Deficiency, GATM Deficiency) is caused by mutation in the GATM gene, which codes for L-arginine:glycine amidinotransferase, which catalyzes the reaction between L-arginine and glycine, transferring an amidino group from L-arginine to glycine, producing L-ornithine and guanidinoacetate, a precursor of creatine. A defect in this enzyme causes a decrease in concentration of creatine and guanidinoacetate in plasma and urine. Symptoms include mental and motor retardation, seizures, and delayed or abnormal speech development.
References
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency) References
[OMIM: Entry 612718](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=612718)
[Metagene: mp=L-ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY](http://www.metagene.de/program/d.prg?mp=L-ARGININE:GLYCINE%20AMIDINOTRANSFERASE%20DEFICIENCY)
Battini R, Alessandri MG, Leuzzi V, Moro F, Tosetti M, Bianchi MC, Cioni G: Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. J Pediatr. 2006 Jun;148(6):828-30. doi: 10.1016/j.jpeds.2006.01.043.
Pubmed: 16769397
Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, Tosetti M, Fornai F, Cioni G: Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Nov;69(5):1127-33. doi: 10.1086/323765. Epub 2001 Sep 10.
Pubmed: 11555793
Schulze A: Creatine deficiency syndromes. Mol Cell Biochem. 2003 Feb;244(1-2):143-50.
Pubmed: 12701824
Verma A: Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy. Neurology. 2010 Jul 13;75(2):186-8. doi: 10.1212/WNL.0b013e3181e7cabd.
Pubmed: 20625172
Battini R, Alessandri MG, Casalini C, Casarano M, Tosetti M, Cioni G: Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. Orphanet J Rare Dis. 2017 Feb 2;12(1):21. doi: 10.1186/s13023-017-0577-5.
Pubmed: 28148286
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
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Pubmed: 6194510
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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
Hu CA, Lin WW, Valle D: Cloning, characterization, and expression of cDNAs encoding human delta 1-pyrroline-5-carboxylate dehydrogenase. J Biol Chem. 1996 Apr 19;271(16):9795-800. doi: 10.1074/jbc.271.16.9795.
Pubmed: 8621661
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Pubmed: 14702039
Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. doi: 10.1038/nature04727.
Pubmed: 16710414
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Pubmed: 15662599
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Pubmed: 11891283
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Pubmed: 9385373
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Pubmed: 25865492
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