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Several countries include medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, a rare autosomal recessive disease, in their newborn screening programmes despite prevalence uncertainty. We estimated the frequency of its most common mutation, c.985A>G, tested for regional differences and compared screening and genotype frequencies. We identified 43 studies reporting the frequency of c.985A>G over 10 million individuals, and pooled frequency data using a novel Bayesian approach. We found significant variation in the frequency of the mutation across regions supporting a reported founder effect. The proportion of c.985A>G homozygotes was highest in Western Europe with 4.1 (95%CI: 2.8-5.6) per 100,000 individuals, then the New World (3.2, 95%CI: 2.0-4.7), Southern (1.2, 95%CI: 0.6-2.0) and Eastern European regions (0.9, 95%CI: 0.5-1.7). No cases with the mutation were identified in Asian and Middle Eastern regions. Significant differences were found in some countries between the genotype and screening allele frequency of c.985A>G. Our predictions could inform the frequency of the mutation by region and our approach could apply to other genetic conditions.

Original publication




Journal article


Clin Genet

Publication Date





253 - 259


MCAD deficiency, c.985A>G, inborn errors of metabolism, medium-chain acyl-CoA dehydrogenase deficiency, Acyl-CoA Dehydrogenase, Alleles, Europe, Gene Frequency, Genetic Heterogeneity, Genetic Testing, Genotype, Genotyping Techniques, Homozygote, Humans, Infant, Newborn, Lipid Metabolism, Inborn Errors, Mutation, Neonatal Screening, Odds Ratio