GABA-Transaminase Deficiency

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/gaba-transaminase-deficiency

GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy.

genetic conditions

1. Introduction

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.

2. Frequency

GABA-transaminase deficiency is a very rare disorder. Only a small number of affected individuals have been described in the medical literature.

3. 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.

4. 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.

5. 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

References

Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE.Personalized medicine approach confirms a milder case of ABAT deficiency. MolBrain. 2016 Dec 1;9(1):93.
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.
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. 2016Sep;39(5):743-747. doi: 10.1007/s10545-016-9951-z.
Medina-Kauwe LK, Tobin AJ, De Meirleir L, Jaeken J, Jakobs C, Nyhan WL, GibsonKM. 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J InheritMetab Dis. 1999 Jun;22(4):414-27. Review.
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 compoundheterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene. Brain Dev.2017 Feb;39(2):161-165. doi: 10.1016/j.braindev.2016.08.005.
Pearl PL, Gibson KM. Clinical aspects of the disorders of GABA metabolism inchildren. Curr Opin Neurol. 2004 Apr;17(2):107-13. Review.
Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitterdisorders. J Child Neurol. 2007 May;22(5):606-16. Review.
Pearl PL, Wallis DD, Gibson KM. Pediatric neurotransmitter diseases. CurrNeurol Neurosci Rep. 2004 Mar;4(2):147-52. Review.
Tsuji M, Aida N, Obata T, Tomiyasu M, Furuya N, Kurosawa K, Errami A, GibsonKM, Salomons GS, Jakobs C, Osaka H. A new case of GABA transaminase deficiencyfacilitated by proton MR spectroscopy. J Inherit Metab Dis. 2010 Feb;33(1):85-90.doi: 10.1007/s10545-009-9022-9.

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Subjects: Genetics & Heredity

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Camila Xu

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Entry Collection: MedlinePlus

Update Date: 23 Dec 2020

Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The gene associated with GABA-transaminase deficiency

4. Inheritance

5. Other Names for This Condition

References