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Fatty Acid Oxidation Disorders


Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Fatty acid oxidation disorders are lipid metabolism disorders that are caused by a lack or deficiency of the enzymes needed to break down fats, resulting in delayed mental and physical development. Fatty acid oxidation disorders occur when parents pass the defective genes that cause these disorders on to their children.

There are different types of inherited disorders. In fatty acid oxidation disorders, both parents of the affected child carry a copy of the abnormal gene. Because usually two copies of the abnormal gene are necessary for the disorder to occur, usually neither parent has the disorder. (See also Overview of Hereditary Metabolic Disorders.)

Fats (lipids) are an important source of energy for the body. The body’s store of fat is constantly broken down and reassembled to balance the body’s energy needs with the food available. Several enzymes help break down fats so that they may be turned into energy.

Children who have one of these disorders are missing or have a deficiency of the enzymes needed to break down (metabolize) fats. The lack of these enzymes leaves the body short of energy and allows breakdown products, such as acyl-CoA, to accumulate. The enzyme most commonly deficient is medium-chain acyl-CoA dehydrogenase (MCAD). Other enzyme deficiencies include short-chain acyl-CoA dehydrogenase (SCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, glutaric acidemia type II, and mitochondrial trifunctional protein (TFP) deficiency. Most of these disorders begin in infancy.

Treatment of fatty acid oxidation disorders varies depending on the type of fatty substances that accumulate in the blood and tissues.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

This disorder is one of the most common inherited disorders of metabolism, particularly among people of Northern European descent.

Symptoms of MCAD deficiency usually develop after 2 to 3 months of age. Children are most likely to develop symptoms if they go without food for a period of time (which depletes other sources of energy) or have an increased need for calories because of exercise or illness. The level of sugar (glucose) in the blood drops significantly (hypoglycemia), causing confusion or coma. Children become weak and may have vomiting or seizures. Over the long term, children have delayed mental and physical development, an enlarged liver, heart muscle weakness, and an irregular heartbeat. Sudden death may occur.

Since 2007, nearly every state in the United States has required that all newborns be screened for MCAD deficiency with a blood test. Tests of the urine and other tissues may also be done. DNA testing can be done to confirm the diagnosis.

Immediate treatment of an MCAD deficiency attack is with dextrose given by vein. For long-term treatment, children must eat often, never skip meals, and consume a diet high in carbohydrates and low in fats. Supplements of the amino acid carnitine may be helpful. Cornstarch may need to be given at night to prevent the level of glucose in the blood from getting too low. The long-term outcome is generally good.

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency

This deficiency is the second most common fatty acid oxidation disorder. It causes symptoms similar to those caused by MCAD deficiency. People may also have progressive impairment of the structure and function of the muscular walls of the heart chambers (cardiomyopathy), damage to the nerves of the hands and feet, and abnormal liver function. When children exert themselves, such as when exercising, the muscle tissue may become destroyed (rhabdomyolysis) and the damaged muscles may release the protein myoglobin, which turns the urine brown or bloody (myoglobinuria).

A woman whose fetus has LCHAD deficiency often has hemolysis (the breakdown of red blood cells), elevated levels of liver enzymes (indicating liver damage), and a low platelet count (called HELLP syndrome) while pregnant.

Doctors diagnose LCHAD deficiency by testing the blood for certain acids. Tests of skin cells are done to look for levels of certain enzymes. Genetic testing, which is used to determine whether a couple is at increased risk of having a baby with a hereditary genetic disorder, is also available.

Immediate treatment of an LCHAD deficiency attack is with hydration and glucose given by vein, bed rest, and supplements of the amino acid carnitine. For long-term treatment, children must eat often, avoid strenuous exercise, and consume a diet high in carbohydrates. Children are also given supplements of triglycerides.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency

This deficiency is similar to LCHAD deficiency, but people typically have severe cardiomyopathy.

Glutaric acidemia type II

Children who have this disorder have low blood sugar when their stomach is empty (called fasting hypoglycemia), a severe buildup of acid in the blood (metabolic acidosis), and an increase in ammonia in the blood (hyperammonemia).

Doctors diagnose glutaric acidemia type II by analyzing the blood to look for a buildup of certain molecules. Tests of skin cells are done to look for levels of certain enzymes. Genetic testing is also available.

Treatment of glutaric acidemia type II is similar to that for MCAD deficiency, except that doctors may give supplements of riboflavin (vitamin B2).

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