The inherited disorders of γ-amino butyric acid (GABA) metabolism require an increased index of clinical suspicion. The known genetic disorders are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis. A recent link has also been made between impaired GABA synthesis and nonsyndromic cleft lip, with or without cleft palate. SSADH deficiency is the most commonly occurring of the inherited disorders of neurotransmitters. The disorder has a nonspecific phenotype with myriad neurological and psychiatric manifestations, and usually has a nonprogressive temporal course. Diagnosis is made by the detection of γ-hydroxybutyrate excretion on urine organic acid testing. The most consistent magnetic resonance imaging abnormality is an increased signal in the globus pallidus. Magnetic resonance spectroscopy has demonstrated the first example of increased endogenous GABA in human brain parenchyma in this disorder. GABA-transaminase deficiency and homocarnosinosis appear to be very rare, but require cerebrospinal fluid for detection, thus allowing for the possibility that these entities, as in the other inherited neurotransmitter disorders, are underrecognized. Up to a third of cerebral synapses employ γ-amino butyric acid (GABA), the major inhibitory neurotransmitter of the brain. Its major precursor is L-glutamate, which is converted to GABA via the enzyme glutamate decarboxylase (GAD). GAD has two active isoforms, GAD65 and GAD67. Pyridoxal-5-phosphate is a coenzyme for GAD. GABA is metabolized by the enzyme GABA-transaminase (GABA-T), to succinic semialdehyde. This unstable intermediate compound is metabolized rapidly to succinic acid, which enters the tricarboxylic acid cycle. The so-called GABA shunt is a closed loop that involves the transamination of α-ketoglutarate to glutamate, which is then converted via GAD to GABA (Figure 1). The subsequent transamination of GABA to succinic semialdehyde requires the presence of α-ketoglutarate to accept the amine group. Thus, this restores glutamate and a molecule of the GABA precursor is formed as a molecule of GABA is catabolized. This enables constant replenishment of this vital neurotransmitter pool. There is an ancillary loop, known as the glutamine-glutamate shuttle. Released GABA is taken up by glial cells, where glutamate can be formed, but not converted to GABA, owing to an absence of GAD. Instead, GABA is converted via glutamine synthetase to glutamine, which is returned to the neuron and is converted via glutaminase back to glutamate. Thus, the loop is completed and the supply of GABA precursor is conserved. KeywordsDisorders involving the GABA catabolic pathway are GABA-T deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis; all of these entities invoke neurological dysfunction. SSADH deficiency is the most common, but has a heterogeneous, nonspecific phenotype. Enzymatic deficiency can be documented in SSADH and GABA-T deficiency. Homocarnosine is a dipeptide compound consi...