Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: Clinical, biochemical, and molecular genetic aspects

R. Santer, H. Muhle, T. Suormala, E. R. Baumgartner, M. Duran, X. Yang, Y. Aoki, Y. Suzuki, U. Stephani

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200 mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g > a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalMolecular Genetics and Metabolism
Volume79
Issue number3
DOIs
Publication statusPublished - 2003 Jul 1

Keywords

  • Biotin
  • HLCS
  • Holocarboxylase synthetase
  • Multiple carboxylase deficiency

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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