Frequency of biotinidase gene variants and incidence of biotinidase deficiency in the newborn screening program in minas gerais, brazil

• Autor(a) principal: Nara de Oliveira Carvalho
• Data de Publicação: 2019
• Outros Autores: José Nélio Januário, Gilsimary Lessa Pereira Felix, Daniela Magalhães Nolasco, Roberto Vagner Puglia Ladeira, Dora Mendes Del Castillo, Ana Lúcia Pimenta Starling, Rocksane de Carvalho Norton, Marcos Borato Viana
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: http://hdl.handle.net/1843/55316; https://orcid.org/0000-0002-0912-3782
• topic: Biotinidase; Biotinidase deficiency; Newborn screeenig; Biotinidase gene; Mutation; Biotinidase; Deficiência de Biotinidase; Mutação; Recém nascido

Objective: The prevalence of biotinidase deficiency and the frequency of biotinidase gene variants in Brazil are not docu mented. 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 biotinidaseactivity based on semi-quantitative assays underwent confirmatory serum tests. The biotinidase gene was sequenced in allconfirmed 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 mostfrequent 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