The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient
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The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient Joannie Hui, Eric Law, Christina Chung, Simon Fung, Patrick Yuen, Nelson Tang Hong Kong, China
Case report
Background: Holocarboxylase synthetase deficiency is an inborn error of biotin metabolism leading to multiple carboxylase deficiency which is often biotin responsive. This disease is believed to be relatively common among the Asian population. Methods: A 6-year-old Vietnamese boy presented with recurrent episodes of severe metabolic acidosis precipitated by intercurrent illnesses. An extensive skin rash was present since the onset of his illness. Multiple carboxylase deficiency was considered a likely diagnosis based on the history and the characteristic skin rash. Results: This diagnosis was later confirmed by urine organic acid and molecular genetic studies. Urine organic acid showed characteristic excretion of glycine conjugates. Serum biotinidase activity was normal. Sequencing of the holocarboxylase synthetase gene revealed the patient being homozygous for a common mutation R508W. The patient showed a dramatic response to biotin within days of its administration. Conclusion: This case illustrates a potential highly treatable inborn error of metabolism that can be recognized on clinical grounds and its favorable response to biotin treatment.
Introduction
H
olocarboxylase synthetase (HLCS; EC 6.3.4.10)[1] is an enzyme which is responsible for biotinylation of several biotin-dependent carboxylases in the mitochondria, including pyruvate carboxylase, propionyl-CoA carboxylase and methylcrotonyl-CoA carboxylase. An autosomal recessive inherited deficiency of HLCS leads to multiple carboxylase deficiency (MCD, MIM: 253270). [2] As a result of defective biotinylation of carboxylase enzymes, there is increased excretion of metabolites like 3-methylcrotonylglycine, 3-hydroxyisovaleric and 3 hydroxypropionic acids in the urine. Other than HLCS deficiency, biotinidase deficiency is another enzyme defect that can cause multiple carboxylase deficiency leading to the same abnormal organic acid profile as that in HLCS deficiency. Both enzyme defects (HLCS and biotinidase) can be treated with high dose of biotin and the response to treatment is usually good. Here we report the first case of Vietnamese origin which has been worked up with molecular genetic analysis. This information should be useful for the mutation analysis of future similar patients.
World J Pediatr 2012;8(3):278-280 Key words: biotin; biotinidase deficiency; HLCS gene; holocarboxylase synthetase deficiency; inborn error of metabolism; multiple carboxylase deficiency; rash Author Affiliations: Department of Pediatrics (Hui J, Chung C, Yuen P), Joint Metabolic Clinic (Hui J, Law E, Chung C, Tang N), and Department of Chemical Pathology (Law E, Fung S, Tang N), Prince of Wales Hospital, The Chinese University of Hong Kong, China Corresponding Author: Joannie Hui, Department of Pediatrics, The Chinese University of Hong Kong, China (Email: joan
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