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Description
GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures (epilepsy), uncontrolled limb movements (choreoathetosis), exaggerated reflexes (hyperreflexia), weak muscle tone (hypotonia), and excessive sleepiness (hypersomnolence). Affected babies may grow faster in length than usual (accelerated linear growth), even though they have feeding problems and may not gain weight as quickly as expected (failure to thrive).
Children with GABA-transaminase deficiency have profoundly impaired development. Most do not achieve normal developmental milestones of infancy such as following others' movement with their eyes or sitting unassisted. Individuals with this disorder usually do not survive past the first 2 years of life, but some live longer into childhood.
Frequency
GABA-transaminase deficiency is a very rare disorder. Only a small number of affected individuals have been described in the medical literature.
Causes
GABA-transaminase deficiency is caused by mutations in the ABAT gene, which provides instructions for making the GABA-transaminase enzyme. This enzyme helps break down a brain chemical (neurotransmitter) called GABA when it is not needed. GABA normally helps slow down (inhibit) brain cell activity when necessary, to prevent the brain from being overloaded with too many signals. For this reason, GABA is called an inhibitory neurotransmitter.
Mutations in the ABAT gene lead to a shortage (deficiency) of functional GABA-transaminase enzyme. As a result, GABA is not properly broken down, so this neurotransmitter and another molecule called beta-alanine accumulate abnormally in brain cells. This accumulation alters the balance between the brain's neurotransmitters, leading to the neurological problems characteristic of GABA-transaminase deficiency. Excess GABA also leads to abnormal release of a protein that is necessary for growth of the body's bones and tissues (growth hormone), resulting in the accelerated linear growth that sometimes occurs in this disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- 4 alpha aminobutyrate transaminase deficiency
- ABAT deficiency
- GABA transaminase deficiency
- GABA transferase deficiency
- GABA-T deficiency
- Gamma aminobutyrate transaminase deficiency
- Gamma aminobutyric acid transaminase deficiency
- Gamma-aminobutyrate transaminase deficiency
- Gamma-aminobutyric acid transaminase deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE. Personalized medicine approach confirms a milder case of ABAT deficiency. Mol Brain. 2016 Dec 1;9(1):93. doi: 10.1186/s13041-016-0273-8. Citation on PubMed or Free article on PubMed Central
- 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. Citation on PubMed or Free article on PubMed Central
- Louro P, Ramos L, Robalo C, Cancelinha C, Dinis A, Veiga R, Pina R, Rebelo O, Pop A, Diogo L, Salomons GS, Garcia P. Phenotyping GABA transaminase deficiency: a case description and literature review. J Inherit Metab Dis. 2016 Sep;39(5):743-747. doi: 10.1007/s10545-016-9951-z. Epub 2016 Jul 4. Citation on PubMed
- 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. doi: 10.1023/a:1005500122231. Citation on PubMed
- Nagappa M, Bindu PS, Chiplunkar S, Govindaraj P, Narayanappa G, Krishnan A, Bharath MM, Swaminathan A, Saini J, Arvinda HR, Sinha S, Mathuranath PS, Taly AB. Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene. Brain Dev. 2017 Feb;39(2):161-165. doi: 10.1016/j.braindev.2016.08.005. Epub 2016 Sep 3. Citation on PubMed
- Pearl PL, Gibson KM. Clinical aspects of the disorders of GABA metabolism in children. Curr Opin Neurol. 2004 Apr;17(2):107-13. doi: 10.1097/00019052-200404000-00005. Citation on PubMed
- Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol. 2007 May;22(5):606-16. doi: 10.1177/0883073807302619. Citation on PubMed
- Pearl PL, Wallis DD, Gibson KM. Pediatric neurotransmitter diseases. Curr Neurol Neurosci Rep. 2004 Mar;4(2):147-52. doi: 10.1007/s11910-004-0029-1. Citation on PubMed
- Tsuji M, Aida N, Obata T, Tomiyasu M, Furuya N, Kurosawa K, Errami A, Gibson KM, Salomons GS, Jakobs C, Osaka H. A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. J Inherit Metab Dis. 2010 Feb;33(1):85-90. doi: 10.1007/s10545-009-9022-9. Epub 2010 Jan 6. Citation on PubMed or Free article on PubMed Central
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