Biotin-Responsive Basal Ganglia Disease in Ethnic Europeans With Novel SLC19A3 Mutations

Objective

To report the first 2 European cases of biotin-responsive basal ganglia disease and novelSLC19A3mutations.

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 theSLC19A3disclosed 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.