GABA-Transaminase (GABA-T) deficiency is caused by mutations in the ABAT gene, with individuals affected by different mutations. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell has mutations. In order for someone to be affected by GABA-T deficiency, both copies of the ABAT gene must 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. The recurrence risk in subsequent pregnancies is 25%.
The ABAT gene is responsible for providing instructions for making the GABA-transaminase enzyme. Here the mutations in the ABAT gene affect the production of the GABA-transaminase enzyme, which is responsible for breaking down a chemical called GABA (gamma-aminobutyric acid). GABA is a chemical (neurotransmitter) that normally helps slow down (inhibit) the activity in brain cells, to prevent the brain from being overwhelmed with too many signals. Without the enzyme, there is a build-up of GABA, and the balance of the neurotransmitters in the brain is altered.
GABA-T deficiency is typically diagnosed by testing a sample of cerebrospinal fluid (CSF) for high levels of the amino acid GABA. This is done by removing some of the fluid that surrounds the brain through a lumbar puncture. Whole exome sequencing or ABAT specific gene testing can confirm the diagnosis and involves the collection of a sample of blood. MR spectroscopy with special editing for small molecules has been used recently to diagnose cases as well.