Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

Biotin-responsive basal ganglia disease (BBGD) is an autosomal recessive disorder, which is caused by mutations in the SLC19A3 gene, encoding a thiamin transporter. The disease was first described in 1998 and later genetically characterized in 2005. Most patients reported were of Saudi, Syrian, or Yemeni ancestry. So far, 20 cases have been reported in the literature.

BBGD typically manifests in childhood with symmetrical lesions in the basal ganglia, causing progressive neurological problems including dystonia, dysarthria, and seizures. If untreated, the clinical course may be fatal.

Here we report the case of a 6-year-old girl, born to consanguineous Moroccan parents. She was the third child of the family. Two older sisters suffered from a progressive neurodegenerative disorder, which was classified as Leigh syndrome because of symmetric basal ganglia lesions. However, in these two children, biochemical diagnostics including oxidative phosphorylation system measurement in fresh muscle tissue did not reveal any disturbance of mitochondrial metabolism. Both children died in the course of the disease. Also the above mentioned 6-year-old girl developed symmetric basal ganglia lesions and showed progressive neurological deterioration. Reevaluation of the clinical situation brought up the differential diagnosis BBGD and the girl was treated with high-dose biotin (10 mg/kg/d) and additional thiamine. Medication improved her situation dramatically and molecular genetic studies confirmed BBGD, demonstrating a mutation in the SLC19A3 gene (c.1264G>A, p.T422A). The further clinical course of the girl was favorable. Follow-up brain MRI, 3 months after the acute metabolic crisis revealed a clear regression of basal ganglia lesions.

To conclude, our report highlights that BBGD is an important treatable differential diagnosis of Leigh syndrome. Therefore, Biotin treatment is suggested for any patient with symmetrical basal ganglia lesions and neurological problems until BBGD is excluded or a mitochondrial dysfunction has been clearly identified.