Biotin-responsive basal ganglia disease in a 10-year-old German girl without SLC19A3 gene mutation

Introduction: Biotin-responsive basal ganglia disease is an extremely rare but easily treatable encephalopathy. The condition is associated with mutations in the SLC19A3 gene. We report the first case of this metabolic disease in Central Europe.

Case Report: Following an episode of febrile viral tonsillitis, a 10-year-old previously healthy girl of nonconsanguine German parents developed encephalopathy with symptoms including mutism, severe swallowing problems, external ophthalmoplegia, spastic tetraparesis, and a seizure. T2-weighted MRI showed massive bilateral symmetrically increased signal in the basal ganglia (nucleus caudatus and putamen), in the mesencephalon, and in the occipital cortex. CSF biochemistry, cytology, and immunology, as well as an extensive metabolic, autoimmune, and infectious diseases work-up were normal. Despite therapy with cefotaxime, acyclovir, methyl prednisone, and immunoglobulins, there was no improvement in her condition over 14 days. Within 24 hours of administration of biotin (5 mg/kg/day), she was able to walk independently, and within 2 days, she was able to speak and swallow normally. At follow-up after 2 months, she showed only minor behavioral abnormalities and cognitive testing was normal. A mutation in the SLC19A3 gene was not found.

Discussion: Biotin-responsive basal ganglia disease is characterized by severe episodic encephalopathy, often presenting during the first decade of life and usually following a febrile illness. Bilateral signal alterations in the basal ganglia in T2-weighted MRI are typical. Detection of a mutation in the SLC19A3 gene confirms the diagnosis and there is no known biochemical marker. Despite the absence of evidence for SLC19A3 gene mutation in our patient, we regard her dramatic response to biotin as diagnostic of biotin-responsive basal ganglia disease.

Conclusion: Pediatric patients with encephalopathy and bilateral signal alterations of the basal ganglia in T2-weighted MRI should be offered a therapeutic trial of high-dose biotin after exclusion of other metabolic, autoimmune, and infectious diseases.