Child Neurology: Infantile Biotin Thiamine Responsive Basal Ganglia Disease: Case Report and Brief Review

Abstract

Biotin thiamine responsive basal ganglia disease (BTRBGD) is an inherited autosomal recessive disorder that results from the inability of thiamine to cross the blood-brain barrier. It is considered a treatable condition if vitamin supplementation, most commonly with thiamine and biotin, is initiated early. BTRBGD can present as an infantile form, classical childhood form, or adult Wernicke-like encephalopathy. The infantile form is often the most severe and portends a worse prognosis with high mortality despite vitamin supplementation. We present a two-month-old who presented with irritability, opisthotonos, and abnormal eye movements who was found to have compound heterozygous variants in the SLC19A3 gene inherited in trans, including one known pathogenic intronic variant and a novel variant presumed to be pathogenic. She was therefore diagnosed with infantile BTRBGD. In this report, we discuss the differential for infantile BTRBGD, the clinical and radiologic features of BTRBGD, and describe a rapid, positive response to early vitamin supplementation in an infant with a likely pathogenic novel variant in SLC19A3.

Figure. MRI and MR Spectroscopy Findings in BTRBGD

(A) Axial DWI demonstrating diffusion restriction within the bilateral basal ganglia (arrow) and abnormal signal within the medial thalami. (B) Axial T1 demonstrating hypointensity in the bilateral basal ganglia and medial thalami (arrows). (C) MR spectogram of the basal ganglia lesion illustrating a reduction of NAA (arrow) relative to other metabolites, suggestive of neuronal injury. (D) Axial SWI does not demonstrate abnormal mineralization or hemorrhage (arrow indicating absent mineralization of the basal ganglia). BTRBGD = biotin thiamine responsive basal ganglia disease.