Enzymatic and immunological demonstration of normal and defective succinic semialdehyde dehydrogenase activity in fetal brain, liver and kidney

Succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.24) deficiency (McKusick 271980) is an inborn error of 4-aminobutyric acid (GABA) metabolism. The enzymatic defect blocks the oxidation of succinic semialdehyde (SSA) to succinic acid, resulting in conversion of SSA to 4-hydroxybutyric acid (gamma-hydroxybutyric acid, GHB), which accumulates in patients' physiological fluids. SSADH-deficient patients present with variable retardation of intellectual, motor and speech development, often accompanied by ataxia and hypotonia (Jakobs et al 1993a). Prenatal diagnosis of SSADH deficiency, associated with elevated GHB in amniotic fluid and deficient SSADH activity in cultured amniocytes, has been reported (Jakobs et al 1993b). The present communication extends these findings by reporting SSADH deficiency in affected fetal brain, liver and kidney, representing the first demonstration of SSADH deficiency in brain and SSADH expression in normal human liver and kidney.