title: Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation.
abstract: Holocarboxylase synthetase (HCS) is responsible for the biotinylation of pyruvate carboxylase, propionyl coenzyme A (CoA) carboxylase, beta-methylcrotonoyl CoA carboxylase, and acetyl CoA carboxylase. We report on a patient with HCS deficiency resulting in a rare metabolic disease. The patient, a 2-year-old boy, presented with vomiting, consciousness disturbance, and dyspnea. Laboratory examinations showed hyperglycemia, hyperammonemia, lactic acidosis, and excretion of large amounts of beta-hydroxyisovalerate and beta-methylcrotonylglycine in the urine. After 10 days of treatment with biotin 5 mg.kg-1.day-1, the abnormal organic acids in his urine had almost completely disappeared. There were no subsequent attacks, and his growth and development remained normal during 1 year of follow-up. Nucleotide sequence analysis of the HCS cDNA of the patient revealed a homozygous 1809C-->T (R508W) mutation. The R508W mutation is found worldwide, and might be associated with higher residual HCS activity than other mutations. Late-onset HCS deficiency cannot be differentiated clinically from biotinidase deficiency. Prompt and correct diagnosis is important for these biotin-responsive disorders.
authors.affiliation: Department of Pediatrics and Medical Genetics, College of Medicine, National Taiwan University, Taipei.
authors.forename: W L
authors.initials: WL
authors.lastname: Hwu
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: S P
authors.initials: SP
authors.lastname: Chou
authors.forename: K
authors.initials: K
authors.lastname: Narisawa
authors.forename: W Y
authors.initials: WY
authors.lastname: Tsai
mesh_terms: D019731:Carbon-Nitrogen Ligases / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases