Medium-chain acyl-CoA dehydrogenase deficiency: prevalence of ACADM pathogenic variants c.985A>G and c.199T>C in a healthy population in Rio Grande do Sul, Brazil

Objectives::To investigate the prevalence of ACADM pathogenic variants, c.985A>G and c.199T>C, for medium chain acyl CoA dehydrogenase deficiency (MCADD) in a healthy population in the southern region of Brazil. Methods::This was an observational cross-sectional study with a convenience sampling strategy. The participants were recruited from the blood bank of the Hospital de Clínicas of Porto Alegre, Brazil. A total of 1000 healthy individuals from the state of Rio Grande do Sul were included. Genotyping for the c.199T>C and c.985A>G variants was performed using real-time polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism (RFLP) technique, respectively. Individuals considered heterozygous for c.985A>G were subjected to additional acylcarnitine profile analysis using tandem mass spectrometry. Carrier frequency was obtained by calculating the ratio of heterozygous individuals to the total number of individuals analyzed and reported with a 95% confidence interval. Allele and genotype frequencies were calculated based on the Hardy-Weinberg equilibrium.Results::The c.985A>G variant was detected as heterozygotes in three individuals (frequency of the heterozygous genotype = 1:333, allele frequency= 0.0015, minimum frequency of MCADD= 1:444,444) whose acylcarnitine profiles were within normal limits. The c.199T>C variant was not identified.Conclusions::Considering the small sample size and associated allelic heterogeneity with MCADD, these findings are believed to denote the rarity or underdiagnosis of MCADD in southern Brazil. This study provides evidence for the need for further investigation to ascertain the contribution of these diseases to child morbidity and mortality in the country.