Introduction: Thiamine in Wilsons disease (WD) animal models seems to protect against the toxic effects of free copper, including activation of reactive oxygen species, nitric oxide synthetase and decreasing serotonin synthesis (1). Chelation therapy can paradoxically worsen neurological symptoms in upto 30% of patients presumably by increasing free copper (2).

Case: An 8-year-old girl presented with rapidly developing gait difficulty and mild dystonia following a febrile illness. Routine CSF studies, CSF lactate, Tandem Mass Spectroscopy, and biotinidase assay were normal. Symmetrical T2 hyperintense striatal and brainstem lesions with restricted diffusion suggested possible Biotin-Thiamine-Responsive Basal Ganglia Disease (BTRBGD). Biotin / Thiamine led to significant improvement. Persistent MRI abnormalities , low ceruloplasmin and pathogenic mutation in the ATP7B gene confirmed WD. Thiamine was discontinued and zinc and 125 mg penicillamine / day led to significant neurological worsening in 4 days. Gross Motor Functional Classification System  (GMFCS) score slipped from Grade 1 to Grade 4, which persisted for 2 weeks despite penicillamine discontinuation. Thiamine was        re-started and dramatic improvement was noted within 1 week with return to normal by 1 month. Re-analysis of targeted gene panels failed to reveal mutations in the SLC19A3 gene responsible for BTRBGD.

Conclusion.  Thiamine seemed to help in neurological worsening induced by chelation in WD presumably by reducing the deleterious cellular effects of free copper. This requires further study before definite conclusions can be drawn.

1)      Luong K, 2013; J Mol Genet Med ;DOI: 10.4172/1747-0862.1000079

2)      Kalita J  2013; DOI: 10.1159/0003552