Child Neurology: Infantile Biotin Thiamine Responsive Basal Ganglia Disease

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.1-3It is considered a treatable condition if vitamin supplementation, most commonly with thiamine and biotin, is initiated early.2BTRBGD can present as an infantile form, classical childhood form, or adult Wernicke-like encephalopathy.3The 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.

Biotin-thiamine responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of cases in Kuwait with novel variants

“…All detected variants were inherited from asymptomatic parents that are heterozygous for the pathogenic variant. Figure 1 a is a schematic showing the location of all the SLC19A3 variants identified in this study on the six-exon gene structure, in addition to all SLC19A3 variants reported in the literature [ 6 , 12 , 17 – 19 ].…”

Identification of novel mutations in TPK1 and SLC19A3 genes in families exhibiting thiamine metabolism dysfunction syndrome

“…Patients with SLC19A3 deficiency usually have normal psychomotor development until the first episode of encephalopathy, which infections could trigger. The characteristics of BTRBGD are early onset encephalopathy, seizure, ataxia, bulbar dysfunction, and dystonia/hypotonia [ 20 ]. Brain MRI is abnormal in all symptomatic cases, and usually symmetrically distributed lesions could be seen, especially in caudate nuclei, putamen, and medial thalami.…”

An unusually mild case of biotin-thiamine-responsive basal ganglia disease

“…Maney et al recently described a case of BTBGD diagnosed very early in a 2-month-old infant [ 8 ]. Our case emphasizes that BTBGD is a condition that can present with a milder, later-onset phenotype, further adding to the understanding of the disease spectrum.…”