Objective: The prevalence of biotinidase deficiency and the frequency of biotinidase gene variants in Brazil are not documented. We aimed to determine the incidence of partial and profound biotinidase deficiency in the state of Minas Gerais, Brazil, and to calculate the frequency of biotinidase gene variants in the newborn screening program of Minas Gerais.
Methods: Neonates (1,168,385) were screened from May 2013 to June 2018. Those detected with abnormal biotinidase activity based on semi-quantitative assays underwent confirmatory serum tests. The biotinidase gene was sequenced in all confirmed cases.
Results: The combined incidence of partial and profound biotinidase deficiency was estimated at 1:13,909 live births (95% confidence limit 1:11,235-1:17,217), much higher than the incidence rates reported in other populations worldwide. The most frequent biotinidase gene variants were p.D444H (allele frequency, 0.016), haplotype c.1330G>C;c.511G>A (p.D444H;A171T), p.D543E, c.310-15delT (intronic), p.V199M, and p.H485Q. Together these accounted for 74.6% of the alleles analysed.
Conclusion: Newborn screening for biotinidase deficiency, which revealed a higher incidence in Minas Gerais, is feasible and plays a critical role in the early identification of affected neonates and prevention of symptoms and irreversible sequelae. Biotinidase gene sequencing is a useful tool to confirm the diagnosis, and also provides valuable information about genetic variability among different populations.
Keywords: Biotinidase; biotinidase deficiency; biotinidase gene; mutation; newborn screening.