title: A fluorimetric assay for succinic semialdehyde dehydrogenase activity suitable for prenatal diagnosis of the enzyme deficiency.
abstract: Succinic semialdehyde dehydrogenase (SSAD) is an enzyme involved in the turnover of the neurotransmitter 4-aminobutyrate (GABA). Deficiency of SSAD results in developmental delay, ataxia, seizures and 4-hydroxybutyric aciduria. We have developed a simple fluorimetric assay for the enzyme and applied it to measurement of SSAD activity in a range of cell types often used for prenatal and postnatal diagnosis of enzyme defects. Lymphocytes from children with SSAD deficiency were found to have < 5% of the activity found in lymphocytes from normal children. Heterozygotes are asymptomatic and have intermediate enzyme activities. Although SSAD activity has been detected previously in uncultured chorionic villi, we found that SSAD was not expressed in cultured chorionic villus cells nor in some fibroblast-like amniocytes from control fetuses. Lymphocytes from fetal blood and non-fibroblastic amniocytes have high SSAD activities, and should be suitable for prenatal diagnosis of SSAD deficiency.
authors.affiliation: Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Parkville, Melbourne, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: G N
authors.initials: GN
authors.lastname: Thompson
authors.forename: D W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000293:Adolescent; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000032:analysis* / Q000097:blood / Q000172:deficiency*; D000650:Amnion / Q000166:cytology / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D002824:Chorionic Villi / Q000201:enzymology; D005260:Female; D005312:Fetal Blood / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000201:enzymology; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D013050:Spectrometry, Fluorescence; D050644:Succinate-Semialdehyde Dehydrogenase
chemical_list: D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase