title: Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism.
abstract: Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 +/- 1.9 pmol . min-1 . mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol . min-1 . mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000097:blood; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000097:blood / Q000172:deficiency*; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D002262:Carboxy-Lyases / Q000097:blood; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase; D009243:NAD / Q000097:blood; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000097:blood*
chemical_list: D009243:NAD; D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase; D000612:4-Aminobutyrate Transaminase; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase