MCAD deficiency is an autosomal recessive inherited disorder of ß-oxidation of fatty acids. A study of over 930,000 newborns in the U.S. found an incidence of 1:15,000. Previous estimates for the Caucasian population are in the same range. It is probably the most common disorder of fatty acid metabolism of all. The disease is characterized by intolerance to periods of fasting. Homozygous carriers often become ill in infancy after periods of fasting due to viral infections. They typically suffer from repeated vomiting, hypoketotic hypoglycemia, and are lethargic to comatose. In rare cases, the disease can also lead to sudden infant death syndrome. Biochemical diagnosis can be made by determination of acetylcarnithine in the blood. MCAD deficiency is nowadays detected in most cases as part of newborn screening by tandem mass spectrometry.
MCAD deficiency is caused by pathogenic variants in the medium-chain acyl-CoA dehydrogenase gene (ACADM). The most common causative variant, leading to amino acid substitution Lys329Glu, is detectable in approximately 90% of alleles from patients with MCAD deficiency. In most patients this variant is homozygous, in about 1/5 of patients it is present in a combined heterozygous form with another variant. Therapeutically, periods of fasting should be strictly avoided by regular meals.
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