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Eur J Pediatr. 2000 Jan-Feb;159(1-2):18-22.

Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency.

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Department of Medical Genetics (Biochemical Genetics), Tohoku University School of Medicine, Sendai, Japan.


Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabolism characterised by metabolic ketoacidosis and skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this disease is usually between the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the patient developed his first episode of acidosis at age 8 years and had an exceptionally slow response to biotin therapy. A homozygous mutation was identified at the + 5 position of the splice donor site in intron 10 of the HCS gene (IVs10 + 5(g-->a)), resulting in abnormal splicing of HCS mRNA. A moderate decrease in the amount of normal HCS mRNA may account for the atypical, late-onset phenotype of this patient. Conclusion Molecular analysis is a useful tool for understanding the phenotypic variations in holocarboxylase synthetase deficiency.

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