Defective succinic semialdehyde dehydrogenase activity in 4-hydroxybutyric aciduria

Succinic semialdehyde dehydrogenase deficiency has been demonstrated in a fourth patient with 4-hydroxybutyric aciduria. Lysates of freshly isolated lymphocytes and cultured lymphoblasts of the patient had much lower than control activity in the conversion of U-¹⁴C-4-aminobutyric acid to ¹⁴C-succinic acid in an assay designed to estimate succinic semialdehyde dehydrogenase utilizing endogenous 4-aminobutyrate transaminase. Lymphocyte and lymphoblast lysates of the patient accumulated U-¹⁴C-succinic semialdehyde when incubated with U-¹⁴C-4-aminobutyric acid and NAD⁺ whereas none could be detected in controls. Assays using U-¹⁴C-succinic semialdehyde as substrate for succinic semialdehyde dehydrogenase in lysates of cultured lymphoblasts characterized the patient as having a severe deficiency of succinic semialdehyde dehydrogenase. The data indicate that defective activity of succinic semialdehyde dehydrogenase is responsible for 4-hydroxybutyric aciduria.