Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene

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Abstract
Medium chain acyl‐CoA dehydrogenase (MCAD) catalyzes the first reaction of the β‐oxidation cycle for 4‐10‐carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A→G, was found in 90% of 344 variant alleles. 985A→G causes glutamate substitution for lysine‐304 in the mature MCAD subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl‐CoA dehydrogenase gene family, the structure of the MCAD gene and the evolution of 985A→G mutation are briefly discussed.