[Medium-chain acyl-CoA dehydrogenase deficiency: contribution of molecular biology]

Medium-chain acyl-CoA dehydrogenase deficiency is the most frequent cause of defective congenital fatty acid oxidation. Its molecular characterization is now possible. Case n. 1. A girl, 15 month-old, was admitted because she suffered from fever and vomiting, requiring the administration of aspirin. One day later, she showed signs of drowsiness and hypotonia; her blood glucose concentration was 0.3 g/l. She was given intravenous glucose and this episode rapidly passed. Case n. 2. A boy, brother of the preceding patient, was routinely investigated; he was never symptomatic. Case n. 3. A boy, sibling of the two preceding children, was admitted at the age of 18 months because he had gone into a coma during a febrile episode. His blood glucose concentration was 0.15 g/l. This episode was rapidly resolved by a glucose infusion. His fasting blood concentrations of glucose, non esterified fatty acids. beta-hydroxybutyrate, lactate and pyruvate were normal as were his blood carnitine and ammonia, but he showed elevated urinary excretion of dicarboxylic acids.

Genomic DNA was extracted from peripheral leukocytes of the three sibs and their parents. The A-->G mutation at nucleotide 985 of the MCAD gene was detected by amplification and creation of a restriction site (ACRS). The implicated segment of this gene was amplified by PCR.

ACRS showed that the symptomatic children were homozygous for the A-->G mutation, whereas their parents were heterozygous. The third asymptomatic child did not carry the mutation.

Molecular biology techniques are appropriate for diagnosing this potentially lethal disease and their use for screening is important for disease prevention.