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

Holocarboxylase synthetase (HCS) deficiency is a disorder of biotin metabol ism characterised by metabolic ketoacidosis and skin lesions due to reduced activities of multiple biotin-dependent carboxylases. The onset of this di sease is usually between the neonatal and infantile period. Here we report the molecular analysis of an atypical case of HCS deficiency, where the pat ient developed his first episode of acidosis at age 8 years and had an exce ptionally slow response to biotin therapy. A homozygous mutation was identi fied at the +5 position of the splice donor site in intron 10 of the HCS ge ne (IVs10 + 5(g --> a)), resulting in abnormal splicing of HCS mRNA. A mode rate 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 phenot ypic variations in holocarboxylase synthetase deficiency.