Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations

Arch Neurol. 2010 Jan;67(1):126-30. doi: 10.1001/archneurol.2009.293.

Abstract

Objective: To report the first 2 European cases of biotin-responsive basal ganglia disease and novel SLC19A3 mutations.

Design: Case reports.

Setting: University hospital. Patients A 33-year-old man and his 29-year-old sister, both of Portuguese ancestry, presented with recurrent episodes of encephalopathy. Between episodes patients exhibited generalized dystonia, epilepsy, and bilateral hyperintensities of the caudate and putamen.

Main outcome measures: Clinical and radiologic findings.

Results: Administration of high doses of biotin or of a combination of biotin and thiamine during encephalopathies resulted in spectacular clinical and radiologic improvement in both patients. Sequencing of the SLC19A3 disclosed 2 novel mutations, both of which created premature stop codons in the protein sequence of hTHTR2.

Conclusion: This study demonstrates that biotin-responsive basal ganglia disease is a panethnic condition. A therapeutic trial with high doses of biotin and thiamine seems mandatory in every unexplained encephalopathy with bilateral lesions of putamen and caudate nuclei.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism
  • Basal Ganglia / pathology
  • Basal Ganglia Diseases / drug therapy*
  • Basal Ganglia Diseases / genetics*
  • Basal Ganglia Diseases / metabolism
  • Biotin / pharmacology*
  • Biotin / therapeutic use
  • Brain Diseases, Metabolic / drug therapy*
  • Brain Diseases, Metabolic / genetics*
  • Brain Diseases, Metabolic / metabolism
  • DNA Mutational Analysis
  • Dystonia / genetics
  • Epilepsy / genetics
  • Europe / ethnology
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Membrane Transport Proteins / genetics*
  • Mutation / genetics*
  • Portugal / ethnology
  • Thiamine / pharmacology
  • Thiamine / therapeutic use
  • Treatment Outcome
  • Vitamin B Complex / pharmacology*
  • Vitamin B Complex / therapeutic use
  • White People / genetics

Substances

  • Genetic Markers
  • Membrane Transport Proteins
  • SLC19A3 protein, human
  • Vitamin B Complex
  • Biotin
  • Thiamine