MCADD is inherited in an autosomal recessive manner, meaning an affected individual must inherit a mutated allele from both of their parents. ACADM is the gene involved, located at 1p31, with 12 exons and coding for a protein of 421 amino acids. There is a common mutation among Northern European Caucasians, replacement of an adenine at position 985 with guanine, which results in a substitution of lysine with glutamic acid at position 304 of the protein. Other mutations have been identified more commonly since newborn screening has expanded the mutation spectrum. The 985A>G common mutation is present in the homozygous state in 80% of Caucasian individuals who presented clinically with MCADD and in 60% of the population identified by screening. An individual's genotype does not correlate well with their clinical phenotype for MCADD. The clinical presentation of an individual with MCADD depends not only on the presence of the mutations in the ACADM gene, but also on the presence of environmental or physiological stressors that require the body to depend on fatty acid oxidation for energy. Some mutations, identified through newborn screening programs and associated with higher residual enzyme activity have not been seen in individuals with clinical symptoms of MCADD. Despite this, treatment with fasting avoidance remains the norm for all those diagnosed with MCADD.
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Short-chain acyl-coenzyme A dehydrogenase deficiency
Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
Very long-chain acyl-coenzyme A dehydrogenase deficiency
Holocarboxylase synthetase deficiency
2,4 Dienoyl-CoA reductase deficiency
Systemic primary carnitine deficiency
Malonyl-CoA decarboxylase deficiency