Acyl-CoA Dehydrogenase (Medium Chain)

Definition

Definition of Acyl-CoA Dehydrogenase (Medium Chain)
Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a fatty acid oxidation disorder associated with inborn errors of metabolism. It is due to defects in the enzyme complex known as medium-chain acyl dehydrogenase (MCAD) and reduced activity of this complex. This complex oxidizes medium chain fatty acids (Fatty acids having 6-12 carbons) while reducing FAD to FADH2.

Genetics

Genetics of Acyl-CoA Dehydrogenase (Medium Chain)
Mutations in the ACADM gene lead to inadequate levels of the medium-chain acyl-coenzyme A dehydrogenase enzyme. This condition is inherited in an autosomal recessive pattern, which means two copies of the faulty gene in each cell are required for the disorder to be inherited. If only one copy of the faulty gene is inherited, the individual is a carrier, but does not have the disorder.

Many mutations have been identified in affected patients, but by far the most common mutation is the A985G mutation, in which an adenine is replaced with a guanine on position 985 of the cDNA. Even among patients homozygous for this mutation, however, there is a wide spectrum of disease severity, ranging from asymptomatic to lethal. In some instances, asymptomatic siblings have been diagnosed with MCAD deficiency after a child's diagnosis.

Causes

Causes of Acyl-CoA Dehydrogenase (Medium Chain)
MCADD occurs when an enzyme, called “medium chain acyl-CoA dehydrogenase” (MCAD), is either missing or not working properly. This enzyme’s job is to break down certain fats in the food we eat into energy. It also breaks down fat already stored in the body.

Diagnosis

Diagnosis of Acyl-CoA Dehydrogenase (Medium Chain)
In individuals that have reduced activity of MCAD, there is an impairment of fatty acid oxidation. Under conditions of health this may not cause significant problems. However, when such individuals do not eat for prolonged periods or have increased energy requirements, the impairment of fatty acid oxidation may lead to fatty acid buildup, hypoglycemia, hyperammonemia, and, possibly, sudden death. First symptoms of such an episode, termed a "metabolic crisis," are vomiting and lethargy, and typically present before the onset of hypoglycemia. 20-25% of undiagnosed cases are fatal, and many survivors are left with severe brain damage after particularly severe crises.

Treatment

Treatment of Acyl-CoA Dehydrogenase (Medium Chain)
There is no cure for MCADD, but once diagnosed, adverse effects can be prevented by proper management. The most important part of treatment is to ensure that patients never go without food for longer than 10–12 hours (a typical overnight fast). Patients with an illness causing loss of appetite or severe vomiting may need intravenous glucose to make sure that the body is not dependent on fatty acids for energy. Patients also usually adhere to a low-fat diet. Patients may also take daily doses of carnitine, which helps reduce toxic accumulation of fatty acids by forming acylcarnitines, which are excreted in the urine. Severity of symptoms seems to decrease after puberty, but crises may be brought about by particularly long fasts or heavy alcohol consumption.

Prognosis

Prognosis of Acyl-CoA Dehydrogenase (Medium Chain)
Consult with your doctor.

Prevention

Prevention of Acyl-CoA Dehydrogenase (Medium Chain)
MCADD can also be confirmed either by a blood test called an acylcarnitine profile or an enzyme test on a skin sample. Talk to your doctor or your genetic counselor if you have questions about testing for MCADD.