Unresponsiveness to Vitamin Therapy in Twins with Early Onset Biotin-Thiamine Responsive Encephalopathy Type 2 Caused by Biallelic Truncating Variant in SLC19A3 Gene

Biotin-thiamine responsive encephalopathy type 2 (BTBGD) is caused by biallelic pathogenic variants in SLC19A3 (solute carrier family 19). Among three clinical phenotypes of BTBGD (early infantile onset, classical and adult onset) early infantile form of BTBGD is associated with poor prognosis. Here in we report twins with BTBGD early onset infantile Leigh syndrome phenotype unresponsive to thiamine and biotin therapy, progressive neuroimaging changes and early death. Both twins carried biallelic truncating novel c.307dupG / p.Val103fs*121 variant in SLC19A3 gene and we discuss reasons of unresponsiveness.