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Pathway Description
GABA-Transaminase Deficiency
Homo sapiens
Disease Pathway
GABA-transaminase deficiency, also known as gamma-amino butyric acid transaminase (GABA-T) deficiency, is an extremely rare autosomal recessive inborn error of metabolism (IEM) that is caused by a defect in the ABAT gene, which codes for 4-aminobutyrate (GABA) aminotransferase. This enzyme is present in several tissues in addition to brain and is most active in liver, and it catalyzes the conversion of GABA and 2-oxoglutarate into succinic semialdehyde and L-glutamate, and when it is deficient, GABA levels in the body, specifically the cerebrospinal fluid, are elevated. GABA is a neurotransmitter found in the nervous system that inhibits neurons from firing, and also affects the development of the brain, as well as regulating muscle tone. GABA-T can also convert beta-alanine and oxoglutaric acid to L-glutamic acid and malonic semialdehyde as part of the beta-alanine metabolism pathway, and when it is mutated, leads to an accumulation of beta-alanine within the cell. GABA-T deficiency is characterized by an increase of GABA levels in the cerebrospinal fluid. Symptoms of this disorder include low muscle tone and psychomotor retardation, as well as potential epilepsy and excessive sleeping. Treatment with Flumanezil, sold as Anexate, Lanexat, Mazicon or Romazicon, a GABA-A antagonist, has been tested and may be beneficial in some cases, and potentially more effective if started at a young age. It is estimated that GABA-T deficiency affects less than 1 in 1,000,000 individuals, as only five cases have been reported in literature as of 2017.
References
GABA-Transaminase Deficiency References
[OMIM: Entry 137150](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137150)
[Metagene: id_d=32](http://www.metagene.de/program/d.prg?id_d=32)
[Uniprot: P80404](http://www.uniprot.org/uniprot/P80404)
Bhattacharyya SP, Saha N, Wee KP: gamma-Aminobutyric acid transaminase (GABAT) polymorphism among ethnic groups in Singapore--with report of a new allele. Am J Hum Genet. 1985 Mar;37(2):358-61.
Pubmed: 3985010
Gibson KM, Nyhan WL, Jaeken J: Inborn errors of GABA metabolism. Bioessays. 1986 Jan;4(1):24-7. doi: 10.1002/bies.950040107.
Pubmed: 3790108
Medina-Kauwe LK, Tobin AJ, De Meirleir L, Jaeken J, Jakobs C, Nyhan WL, Gibson KM: 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis. 1999 Jun;22(4):414-27.
Pubmed: 10407778
Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, Ichikawa K, Osaka H, Tsuji M, Gibson KM, Bonnen PE, Pearl PL: Phenotype of GABA-transaminase deficiency. Neurology. 2017 May 16;88(20):1919-1924. doi: 10.1212/WNL.0000000000003936. Epub 2017 Apr 14.
Pubmed: 28411234
beta-Alanine Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Schnuck JK, Sunderland KL, Kuennen MR, Vaughan RA: Characterization of the metabolic effect of beta-alanine on markers of oxidative metabolism and mitochondrial biogenesis in skeletal muscle. J Exerc Nutrition Biochem. 2016 Jun;20(2):34-41. doi: 10.20463/jenb.2016.06.20.2.5. Epub 2016 Jun 30.
Pubmed: 27508152
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