Succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency, often shortened to SSADH deficiency, is a rare autosomal recessive disorder of the pathway that breaks down gamma-aminobutyric acid (GABA), the brain's main inhibitory neurotransmitter. Normally the enzyme works with GABA transaminase to turn GABA into succinic acid, which feeds the Krebs cycle. When the enzyme is missing, succinic semialdehyde builds up and is reduced to gamma-hydroxybutyric acid (GHB), and the raised GHB is believed to be the hallmark of the disorder and the source of its neurological effects. The first case was identified in 1981 and roughly 350 families have since been described, many of them consanguineous. Features fall into neurological, psychiatric and ocular groups. Developmental delay, hypotonia and intellectual disability are the most constant, and about half of patients show ataxia, behavior problems, seizures and reduced reflexes. Onset ranges from the newborn period to about 25 years, and severity varies widely from case to case.