Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation.
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.
Hwu
W L
WL
Department of Pediatrics and Medical Genetics, College of Medicine, National Taiwan University, Taipei.
Suzuki
Y
Y
Yang
X
X
Li
X
X
Chou
S P
SP
Narisawa
K
K
Tsai
W Y
WY
D019731:Carbon-Nitrogen Ligases / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D006801:Humans; D008297:Male; D009154:Mutation
D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases