GABA-Transaminase Deficiency


GABA-Transaminase Deficiency (Gamma-amino butyric acid transaminase deficiency; GABA-T) is caused by a defect in the gene coding for gamma-aminobutyrate transaminase, which is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. GABAT is present in several tissues in addition to brain and is most active in liver. GABA-T catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. This enzyme can also convert delta-aminovalerate and beta-alanine. Defects in GABA-T cause accumulation of beta-alanine and gamma aminobutyric acid in plasma and spinal fluid, as well as accumulation of homocarnosine in spinal fluid. Symptoms include hyperreflexia, hypotonia, lethargia, macrosomia, mental retardation, and siezures.

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References

  1. OMIM: Entry 137150
  2. Metagene: id_d=32
  3. Uniprot: P80404
  4. 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
  5. Gibson KM, Nyhan WL, Jaeken J: Inborn errors of GABA metabolism. Bioessays. 1986 Jan;4(1):24-7. Pubmed
  6. 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