Medium-chain acyl-CoA dehydrogenase deficiency: postmortem diagnosis in a case of sudden infant death and neonatal diagnosis of an affected sibling.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited disorder of fatty acid oxidation associated with sudden death in infants and, in its fulminant form(s), a Reye-like syndrome. In an 18-month-old female who died suddenly and unexpectedly, the postmortem diagnosis of MCAD deficiency was made by analysis of organic acids, acylglycines, and acylcarnitines and by analysis of the most common mutation causing MCAD deficiency (A985G) in a sample of heart blood obtained at autopsy and frozen at -20 degrees C for 8 months. The patient was homozygous for A985G and metabolites characteristic of MCAD deficiency were identified. Parents and an older sibling were heterozygous for A985G. The mother was 6 months pregnant when the results were known. At the birth of her male infant, blood spot cards and urine were obtained. The infant was homozygous for A985G by analysis of DNA extracted from blood spots and he excreted metabolites characteristic of MCAD deficiency. These results demonstrate the use of novel molecular and metabolite analysis in making the postmortem diagnosis of MCAD deficiency. The neonatal diagnosis of an affected sib permits the institution of appropriate dietary measures to prevent potentially fatal episodes of illness.