[Medium chain acyl-CoA dehydrogenase (MCAD) deficiency: a life-threatening defect of fatty acid oxidation]

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal metabolic disease, which is characterized by non-ketotic hypoglycemia and lethargy. The disease manifests itself by periodic attacks in connection with infections and periods of fasting, or suddenly as unexpected child death or "near miss". Characterization of a prevalent disease-causing mutation (G985) in the MCAD gene has increased the diagnostic possibilities, since 75% of all patients with MCAD deficiency are homozygous for the mutation. Analysis for this mutation in genomic DNA from a bloodspot on a PKU-card constitute today a certain and specific diagnosis for the disease in 75% of all cases. In the remaining 25% the mutation analysis is supplemented with urine metabolite studies by gas chromatography/mass spectrometry, and with measurements of enzyme activities in cultured skin fibroblasts. The disease is today considered more common than previously anticipated, since the incidence of patients with MCAD enzyme deficiency in Denmark is estimated to 1/27,000 newborns, or two new cases annually. The relationship between the enzyme defect (gene defect) and the clinical expression of the disease is a main subject for the clinical research in the disease at present, because less than 10% of all patients with the gene defect are diagnosed. This applies not only to Denmark but also to other countries.