title: Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency.
abstract: The metabolic changes in a patient with succinic semialdehyde dehydrogenase deficiency were investigated following valproate administration using urease pretreatment and gas chromatography-mass spectrometry. A stable isotope dilution technique was used for quantification of urinary 4-hydroxybutyrate. Urinary levels of 4-hydroxybutyrate were 4-fold higher after 1-month valproate therapy. 4,5-Dihydrohexanoate, 2-deoxytetronate and 3-deoxytetronate were also 1.7-2.7-fold higher. The urinary excretions of 4-hydroxybutyrate in valproate non-medicated controls were age dependence and decreased with age. Relationships between 4-hydroxybutyrate excretion and 4-hydroxyvalproate or 5-hydroxyvalproate excretion were observed in valproate medicated controls. It seems that 4-hydroxyvalproate and 5-hydroxyvalproate as well as valproate are involved with increased excretion of 4-hydroxybutyrate following valproate administrations.
authors.affiliation: Division of Human Genetics, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan. shinka@kanazawa-med.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shinka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohfu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.forename: Tomiko
authors.initials: T
authors.lastname: Kuhara
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000652:urine*; D000927:Anticonvulsants / Q000627:therapeutic use*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy / Q000652:urine*; D015203:Reproducibility of Results; D050644:Succinate-Semialdehyde Dehydrogenase; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D014635:Valproic Acid; D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase