The A985 to G mutation of the medium-chain acyl-CoA dehydrogenase gene and sudden infant death syndrome in Normandy

Medium-chain acyl-CoA dehydrogenase deficiency is the most common genetic defect of hepatic fatty acid oxidation. Clinical signs are somnolence and lethargy potentially leading to coma. Death occurs during the first attack in about 20% of cases, suggesting sudden infant death syndrome. A point mutation (adenine to guanine at position 985) in exon 11 of the medium-chain acyl-CoA dehydrogenase gene accounts for 90% of medium-chain acyl-CoA dehydrogenase deficiency-causing alleles. Such a high prevalence of a single mutation makes it possible to estimate the incidence of medium-chain acyl-CoA dehydrogenase deficiency in the general population and in sudden infant death syndrome. The study was performed by polymerase chain reaction amplification from blood spots on filter paper in 2000 randomly selected newborns (group I) and in 225 infants dead from sudden infant death syndrome (group II). Among 2000 newborns, 17 were found to be heterozygote for the G985 mutation. In group 11, one child was found with a single copy of the G985 mutation. So. the estimated frequency of the G985 mutation in the general population was 1/118 and the incidence of medium-chain acyl-CoA dehydrogenase deficiency was calculated as around 1/45 000 in Normandy.