Biallelic loss-of-function variations in BTD cause profound biotinidase deficiency in an Indian patient

Background Biotinidase deficiency (BD) is a rare, autosomal recessive metabolic disorder characterized by neurocutaneous symptoms. This study investigates a case of profound BD in an Indian infant and the underlying genetic basis. Methods A 10-month-old male presenting with seizures, hypotonia, ataxia, visual impairments, and developmental delay underwent biochemical and genetic analysis. Biotinidase activity was measured using an ELISA kit. Sanger sequencing of the biotinidase ( BTD) gene was performed to identify genetic variations. In silico analysis was employed to assess the potential impact of the identified variants. Results The infant biotinidase activity was undetectable and its suggest profound biotinidase deficiency. Novel biallelic loss-of-function variations (c.903G > A and c.946 C > T) in the BTD gene were identified, leading to premature stop codons and truncated, non-functional protein fragments. Conclusion This case expands our knowledge of BD genetic diversity and underscores the critical role of early diagnosis and newborn screening programs in managing this treatable condition.