Gamma-aminobutyric acid transaminase deficiency

Gamma-aminobutyric acid transaminase (GABA-transaminase) deficiency, also known as GABA-T deficiency or 4-aminobutyrate aminotransferase deficiency, is an extremely rare autosomal recessive inborn error of metabolism caused by mutations in the ABAT gene. This enzyme is responsible for the catabolism of GABA, the major inhibitory neurotransmitter in the central nervous system. When GABA-transaminase is deficient, GABA accumulates in the brain and cerebrospinal fluid, leading to severe neurological dysfunction. The condition primarily affects the central nervous system and typically presents in the neonatal or early infantile period. Key clinical features include severe psychomotor retardation, intractable seizures, hypotonia, hyperreflexia, and accelerated linear growth. Affected infants may also exhibit lethargy, feeding difficulties, and a high-pitched cry. Electroencephalographic (EEG) abnormalities are commonly observed. Elevated levels of GABA and beta-alanine can be detected in the cerebrospinal fluid and plasma, which aids in diagnosis. Brain imaging may show abnormalities in white matter. GABA-transaminase deficiency is one of the rarest metabolic disorders ever described, with only a handful of cases reported in the medical literature. There is currently no specific curative treatment. Management is primarily supportive and symptomatic, focusing on seizure control with antiepileptic medications, though seizures are often refractory to standard therapies. Vigabatrin, an irreversible inhibitor of GABA-transaminase, is contraindicated as it would further increase GABA levels. The prognosis is generally poor, with significant morbidity and early mortality reported in most cases.

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