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 on to their children the defective genes that cause these disorders.
There are different types of inherited disorders. In fatty acid oxidation disorders, both parents of the affected child carry 1 copy of the abnormal gene. Because usually 2 copies of the abnormal (recessive) 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 a fatty acid oxidation disorder 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 deficiency (LCHAD), very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), 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 Deficiency (MCADD)
This deficiency is one of the most common inherited disorders of metabolism, particularly among people of Northern European descent.
Symptoms of MCADD 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 time, children have delayed mental and physical development, an enlarged liver, heart muscle weakness, and an irregular heartbeat. Sudden death may occur.
All states in the United States require all newborns be screened for MCADD with a blood test. Tests of the urine and other tissues may also be done. DNA testing can be done to confirm the diagnosis.
The long-term outcome is generally good.
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD)
This deficiency is the second most common fatty acid oxidation disorder. It causes symptoms similar to those caused by MCADD. 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 LCHADD 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 LCHADD 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. All states in the United States require all newborns be screened for LCHADD with a blood test.
Immediate treatment of an LCHADD 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 Deficiency (VLCADD)
This deficiency is similar to LCHADD, 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 acids. Genetic testing is also available.
Treatment of glutaric acidemia type II is similar to that for MCADD, except that doctors may give supplements of riboflavin (vitamin B2) to some people.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
National Organization for Rare Disorders (NORD): This resource provides information to parents and families about rare diseases, including a list of rare diseases, support groups, and clinical trial resources.
Genetic and Rare Diseases Information Center (GARD): This resource provides and easy to understand information about rare or genetic diseases.
