Molecular Diagnosis of Medium-Chain Acyl-CoA Dehydrogenase Deficiency by Oligonucleotide Ligation Assay

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In the current issue of Clinical Chemistry , Romppanen et al. (1) report a molecular screening study in a Finnish population for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, the most common inherited disorder of fatty acid β-oxidation (2). This metabolic disorder, which is transmitted as an autosomal recessive trait, can be regarded as a paradigm for inborn errors of metabolism. As seen in many other genetic disorders, a phenotypic heterogeneity frequently is expressed within the same family, ranging from sudden infant death to asymptomatic individuals (3). The disorder is one of exacerbations and remissions and was initially recognized in children with hypoketogenic hypoglycemia, Reye syndrome, and (or) liver failure, frequently resulting in severe brain damage (2). The pathophysiology of MCAD deficiency involves the inability of cells to oxidize fatty acids 4–12 carbons long. A secondary effect of the metabolic block is systemic carnitine deficiency, further compromising fatty acid metabolism. Thus, clinical attacks are precipitated during fasting or intercurrent illnesses when fat mobilization and fatty acid oxidation are induced. Biochemical markers that are diagnostic of MCAD deficiency include urine hexanoylglycine and phenylpropionylglycine (4) and plasma and urine octanoylcarnitine (5). If the disease is recognized before severe sequelae ensue, conservative treatment results in an excellent prognosis. Therapy involves anticipation and prevention of metabolic decompensation by administration of glucose-containing fluids and l-carnitine. This treatment during an impending catabolic crisis prevents the combination of severe hypoglycemia, dehydration, and metabolic acidosis that might otherwise cause death or …