medium chain acyl-CoA dehydrogenase deficiency

What Is Medium-Chain Acyl-CoA Dehydrogenase Deficiency?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited metabolic disorder in which fats cannot be broken down into energy to fuel the body. It is part of a group of disorders called fatty-acid oxidation defects and is caused by mutations in the ACADM gene. Mutations in this gene lead to low levels of the medium-chain acyl-CoA dehydrogenase enzyme resulting in a buildup of partially metabolized fatty acids that can accumulate in body tissues and cause damage to the brain, liver, and other organs.

For most individuals with MCAD deficiency, symptoms first appear in infancy or early childhood and can be triggered by long periods without eating (fasting) or by illness. Symptoms of metabolic crises include vomiting, lack of energy, low blood sugar, and an enlarged liver. Without treatment, metabolic crises can quickly develop into life-threatening problems including seizures, breathing problems, brain damage, coma, and death. A small percentage of sudden infant death syndrome (SIDS) is likely due to undiagnosed MCAD deficiency. In some cases, symptoms may not appear until late childhood or in adulthood and can be milder.

It is important to note that during the third trimester of pregnancy, complications may occur in women who are carrying a fetus with MCAD deficiency. With fatty-acid oxidation defects, including MCAD deficiency, there is a general risk for HELLP syndrome, which consists of red-blood-cell breakdown (hemolysis), elevated liver enzymes, and low platelet count. There may also be a risk of developing acute fatty liver of pregnancy (AFLP). Symptoms in the mother may only include nausea, vomiting, and abdominal pain, but the underlying issues can be severely problematic and sometimes life-threatening to the mother and fetus if the fetus is not delivered as soon as possible.

How Common Is Medium-Chain Acyl-CoA Dehydrogenase Deficiency?

MCAD deficiency is most common in Caucasians from Northern Europe. In the United States, the disease prevalence is 1 in 17,000 individuals. Affected Americans are often of Northern European ancestry. The disease is rare among Hispanics, African Americans, Asians, and Native Americans in the United States.

Studies have found high rates of MCAD deficiency in Northern Germany (1 in 4,900 individuals) and Southern Germany (1 in 8,500 individuals).

How Is Medium-Chain Acyl-CoA Dehydrogenase Deficiency Treated?

The key treatment for individuals with MCAD deficiency is to avoid fasting. Infants must be frequently fed a formula low in fat but high in carbohydrates. For children and adults, consuming cornstarch can also provide a sustained release of energy and allow for longer gaps between meals. If an individual is unable to eat or drink food on their own, it may be necessary to give them glucose by intravenous fluids.

What Is the Prognosis for an Individual with Medium-Chain Acyl-CoA Dehydrogenase Deficiency?

Early diagnosis and dietary management are crucial for the best outcome. If dietary management starts early (especially before the first crisis) and is consistent, individuals with MCAD deficiency have a good prognosis with normal or near-normal lifespan. In undiagnosed and untreated cases of MCAD deficiency, metabolic crises can quickly cause irreversible damage or even lead to death.