Enzyme analyses with C6-CoA, C6-CoA + C4-CoA, and PP-CoA identified significantly higher residual MCAD enzyme activities in subjects with variant ACADM genotypes when compared to patients with classical ACADM genotypes.After prolonged fasting (range 15-18.5 hours) no hypoglycaemia was observed.
After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycaemia and carnitine supplementation.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism.
Hypoglycemia as one major clinical sign in all fatty acid oxidation defects occurs due to a reduced hepatic glucose output and an enhanced peripheral glucose uptake rather than to transcriptional changes that are also observed simultaneously, as presented in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice.
The cardiac form presents with an early onset cardiomyopathy and a high incidence of infant death, while the hypoglycemic form resembles medium chain acyl-CoA dehydrogenase (MCAD) manifesting with hypoketotic hypoglycemia.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common autosomal recessive disorder of mitochondrial fatty acid oxidation characterized by episodes of hypoketotic hypoglycemia usually beginning in the first 2 y of life.