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

Gurnoor Lail; Susan Blaser; Michal Inbar-Feigenberg

doi:10.1016/j.ymgmr.2023.101004

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

Mol Genet Metab Rep. 2023 Aug 27:37:101004. doi: 10.1016/j.ymgmr.2023.101004. eCollection 2023 Dec.

Authors

Gurnoor Lail¹, Susan Blaser², Michal Inbar-Feigenberg¹

Affiliations

¹ Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
² Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Abstract

Background: Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD) is a treatable neurometabolic condition associated with pathogenic variants in the SLC19A3 gene. The classical childhood-onset phenotype presents at a mean age of 4 years, ranging from birth to 12 years. These patients present with subacute encephalopathy, dysarthria, dysphagia, dystonia, external ophthalmoplegia, seizures, quadriparesis, and even death. Chronically, an MRI brain reveals atrophy and necrosis of the basal ganglia.

Case report: A 16-year-old girl presented in the context of pneumonia with gradual-onset, slowly progressive neurological symptoms. These initial symptoms self-resolved, without treatment with biotin or thiamine, though she had persistent concerns with her writing and memory. MRI brain noted bilateral abnormal signals in the basal ganglia, involving the head and body of the caudate nuclei and the putamen. Whole-exome sequencing (WES) revealed homozygosity for a likely pathogenic variant in the SLC19A3 gene, c.517A > G (p.N173D). Her residual neurological symptoms resolved with biotin and thiamine treatment, with the exception of ongoing memory concerns.

Conclusion: We describe a patient presenting with an atypical form of the classical childhood-onset phenotype of BTBGD. Our case emphasizes that BTBGD is a condition that should be considered as a potential diagnosis in all children, including older children, presenting with the new onset of even minor neurological deficits in the context of illness. It highlights the importance of brain MRI and WES in identifying patients with atypical presentations.

Keywords: Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD); Inborn errors of metabolism (IEM); Leukoencephalopathy; Neurogenetic; Neurometabolic.

Publication types

Case Reports