very-long-chain acyl-CoA dehydrogenase deficiency

What Is Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency?

Very-Long-Chain Acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder caused by mutations in the ACADVL gene. There are three different forms of VLCAD deficiency that range in severity. All three types of VLCAD deficiency are caused by an error in the production of an enzyme called very-long-chain acyl-coenzyme A dehydrogenase. This enzyme is responsible for breaking down a type of fat known as very-long-chain fatty acids and converting it into energy. Individuals with VLCAD deficiency do not have enough of this enzyme and as a result, fats are not converted into energy, leaving an individual with low blood sugar (hypoglycemia) and feelings of weakness or tiredness (lethargy). In addition, a buildup of very-long-chain fatty acids in the body can damage the heart, liver, and muscles, causing additional symptoms of the disease. The symptoms tend to appear during periods of fasting, illness, or exercise.

Early-Onset Form

Infants with the severest form of VLCAD deficiency develop symptoms within the first few months of life. This form of the disease can lead to problems with the heart muscle (cardiomyopathy) or heart rhythm (arrhythmia), which can be life-threatening. Babies with VLCAD deficiency may also have poor muscle tone (hypotonia), low blood sugar, lack of energy, and an enlarged liver (hepatomegaly). Heart problems, metabolic crises, and respiratory issues can lead to early death.

Childhood-Onset Form

This form of VLCAD deficiency often appears in early childhood and does not typically involve the heart. Individuals with the childhood-onset form of VLCAD deficiency typically have an enlarged liver and episodes of low blood sugar. Other liver problems may be present, and some individuals will have muscle weakness and breakdown (rhabdomyolysis).

Late-Onset Form

Individuals with late-onset VLCAD deficiency typically experience mild symptoms beginning in adolescence or adulthood. Some will not experience any symptoms until periods of fasting, illness, or exercise. Late-onset VLCAD deficiency does not typically lead to heart failure, low blood sugar, or metabolic crises. Individuals with this form of the disease may experience occasional periods of muscle cramps and muscle breakdown. This may lead to kidney damage. Symptoms usually worsen after strenuous exercise or other stress.

How Common Is Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency?

VLCAD deficiency has an estimated incidence of 1 in 30,000 to 1 in 100,000 worldwide.

How Is Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency Treated?

Individuals with VLCAD deficiency may be prescribed a special diet. For early-onset VLCAD deficiency, this often includes intravenous glucose and/or a low-fat formula designed with types of fat the individual is better able to metabolize. With early detection and proper treatment, heart issues typically associated with this form of VLCAD deficiency can be avoided. For other forms of VLCAD deficiency, foods high in fat content should be avoided if possible. It is also advisable to avoid long periods between eating (fasting) and very strenuous exercise. Individuals with VLCAD deficiency may need extra medical care during times of illness. Adults who experience muscle breakdown can try to lessen this symptom through adequate hydration and efforts to lower the acidity of the urine to protect the kidneys.

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

In the past, the severe heart problems in early-onset VLCAD deficiency often result in early demise. With early diagnosis and lifelong treatment, however, the prognosis for an individual with VLCAD deficiency is very good. Many are able to live without symptoms and have normal physical and mental development. In milder cases of adult-onset VLCAD deficiency, many individuals remain symptom-free for life even with minimal management.

Additional Considerations for Carriers

Carriers of fatty-acid oxidation defects, including VLCAD deficiency, do not typically show symptoms of the disease. However, there may be an increased risk of serious pregnancy complications, particularly in the third trimester, in women carrying a fetus affected with a fatty-acid oxidation defect. A woman whose pregnancy may be affected by a fatty-acid oxidation defect, such as VLCAD deficiency, should speak with her physician for recommendations and may benefit from consultation with a high-risk physician.