MCADD

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an inherited metabolic disorder of mitochondrial fatty acid beta-oxidation caused by mutations in the ACADM gene, which encodes the medium-chain acyl-CoA dehydrogenase enzyme. It is autosomal recessive. The enzyme normally catalyzes the first step in oxidizing medium-chain fatty acids (approximately C6 to C12) in the liver and other tissues. Deficiency impairs energy production during fasting, leads to accumulation of medium-chain fatty acids and their metabolites, and reduces ketone body formation.

Most affected individuals present in infancy or early childhood with episodes of hypoketotic hypoglycemia, vomiting, lethargy, seizures, liver dysfunction, or coma triggered by fasting or illness. Without prompt treatment, these metabolic crises can cause brain injury or death. Some patients are asymptomatic until a crisis is precipitated by illness or fasting. Newborns detected by screening may remain asymptomatic with proper management.

Diagnosis is commonly made by newborn screening using tandem mass spectrometry, which often shows elevated octanoylcarnitine (C8). Confirmation is by genetic testing for ACADM mutations, with enzyme assays in cells as needed. Biochemical hallmarks include elevated medium-chain acylcarnitines, low or absent ketones during hypoglycemia, and increased dicarboxylic acids in urine.

Management centers on avoiding prolonged fasting and providing regular caloric intake, especially during illness. An emergency plan includes prompt administration of glucose and fluids; hospital observation may be needed if energy balance cannot be maintained. L-carnitine supplementation is used in some cases, though evidence is variable. Long-term dietary management is individualized, often involving regular daytime snacks or nocturnal feeds.

Prognosis varies with early detection and management. MCADD occurs in about 1 in 10,000 to 1 in 20,000 births, with newborn screening and improved crisis care improving outcomes. Untreated crises can be fatal or cause lasting neurologic impairment.