title: [A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase deficiency].
abstract: delta 1-pyrroline 5-carboxylate synthetase (P5C synthetase) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamate semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We described in two siblings a paradoxical hyperammonemia with hypoprolinemia and hypoornithinemia associated to bilateral cataract, mental retardation, joint laxity and skin hyperelasticity. We cloned human P5C synthetase-cDNA by database cloning strategy: this cDNA has an open reading frame of 2,385 bases coding for a polypeptide of 795 amino acids. Both patients are homozygous for an L396S substitution, this amino acid being highly conserved across species. This is the first report of a P5C synthetase deficiency in human.
authors.affiliation: Laboratoire de Biochimie médicale B, URA CNRS 1335, Paris.
authors.forename: P
authors.initials: P
authors.lastname: Kamoun
authors.forename: B
authors.initials: B
authors.lastname: Aral
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency*
chemical_list: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; C494240:ALDH4A1 protein, human; D000587:Oxidoreductases Acting on CH-NH Group Donors
vernacular_title: Une nouvelle maladie héréditaire du métabolisme: le déficit en delta 1-pyrroline 5-carboxylate synthétase.