Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation
Journal
Journal of the Formosan Medical Association
Journal Volume
99
Journal Issue
2
Pages
174-177
Date Issued
2000
Author(s)
Abstract
Holocarboxylase synthetase (HCS) is responsible for the biotinylation of pyruvate carboxylase, propionyl coenzyme A (CoA) carboxylase, β- 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 β- hydroxyisovalerate and β-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.
Subjects
Biotin; Holocarboxylase synthetase; Multiple carboxylase deficiency; R508W mutation
SDGs
Other Subjects
biotinidase; article; case report; chemical analysis; consciousness disorder; disorders of carbohydrate metabolism; dyspnea; enzyme deficiency; gene mutation; human; male; preschool child; sequence analysis; vomiting; Carbon-Nitrogen Ligases; Child, Preschool; Humans; Male; Mutation
Type
journal article