Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency [E71.3]

OMIM numbers: 201450, 607008 (ACADM)

Dr. rer. nat. Christoph Marschall

Scientific Background

MCAD deficiency is an autosomal recessive disorder of the fatty acid β-oxidation. According to a study of more than 930,000 newborns in the USA, the disease has an incidence of 1 in 15,000. Earlier estimations for the Caucasian population suggested a similar number. MCAD is most likely the most common disorder of the fatty acid metabolism. The disease is characterized by a fasting intolerance. Homozygous carriers frequently develop the disease during infancy after periods of fasting due to viral infections. They typically suffer from repetitive vomiting, hypoketotic hypoglycemia and are lethargic or even comatose. In rare cases, the disease may result in sudden infant death. A biochemical diagnosis can be established through determination of acetyl carnitine in the blood. Today, the MCAD deficiency is usually detected during neonatal screenings via tandem mass spectrometry.

MCAD deficiency is caused by mutations in the medium-chain acyl-CoA dehydrogenase gene (ACADM). The most common mutation leading to amino acid substitution Lys329Glu can be detected in 90% of all chromosomes of patients with an MCAD deficiency. In most patients the mutation is found to be homozygous, in approximately 1/5 of all patients compound heterozygous.