Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation

Holocarboxylase synthetase (HCS) is responsible for the biotinylation of py ruvate carboxylase, propionyl coenzyme A (CoA) carboxylase, beta-methylcrot onoyl CoA carboxylase, and acetyl CoA carboxylase. We report on a patient w ith HCs deficiency resulting in a rare metabolic disease. The patient, a 2- year-old boy, presented with vomiting, consciousness disturbance, and dyspn ea. Laboratory examinations showed hyperglycemia, hyperammonemia, lactic ac idosis, and excretion of large amounts of beta-hydroxyisovalerate and beta- methylcrotonylglycine in the urine. After 10 days of treatment with biotin K mg.kg(-1).day(-1), the abnormal organic acids in his urine had almost com pletely disappeared. There were no subsequent attacks, and his growth and d evelopment remained normal during 1 year of follow-up. Nucleotide sequence analysis of the HCS cDNA of the patient revealed a homozygous 1809C-->T (R5 08W) mutation. The R508W mutation is found worldwide, and might be associat ed with higher residual HCS activity than other mutations. Late-onset HCS d eficiency cannot be differentiated clinically from biotinidase deficiency. Prompt and correct diagnosis is important for these biotin-responsive disor ders.