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.
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Authors | W L Hwu, Y Suzuki, X Yang, X Li, S P Chou, K Narisawa, W Y Tsai |
Journal | Journal of the Formosan Medical Association = Taiwan yi zhi
(J Formos Med Assoc)
Vol. 99
Issue 2
Pg. 174-7
(Feb 2000)
ISSN: 0929-6646 [Print] Singapore |
PMID | 10770035
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- Carbon-Nitrogen Ligases
- holocarboxylase synthetases
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Topics |
- Carbon-Nitrogen Ligases
(deficiency, genetics)
- Child, Preschool
- Humans
- Male
- Mutation
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