Carnitine palmitoyltransferase II deficiency

Description

Carnitine palmitoyltransferase II (CPT II) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods of fasting. There are three main types of CPT II deficiency that vary in severity and the age at which symptoms first appear: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.

The lethal neonatal form of CPT II deficiency becomes apparent soon after birth. Infants with this form of the disorder develop respiratory failure, liver failure, a weakened heart muscle (cardiomyopathy), and an irregular heartbeat (arrhythmia). In many cases, the brain and kidneys are also structurally abnormal. Affected individuals have low levels of glucose in the blood and low levels of ketones, which are produced during the breakdown of fats and used for energy. Together, these signs are called hypoketotic hypoglycemia. If affected individuals fast for long periods of time, they can experience seizures or coma. Because of these serious health complications, infants with the lethal neonatal form of CPT II deficiency usually live for only a few days to a few months.

The severe infantile hepatocardiomuscular form of CPT II deficiency affects the liver, heart, and muscles. Signs and symptoms usually appear within the first year of life. This form involves recurring episodes of hypoketotic hypoglycemia, seizures, liver dysfunction, cardiomyopathy, arrhythmia, and muscle weakness (myopathy) in the arms and legs. Signs and symptoms of this form of CPT II deficiency can be triggered by fasting or by illnesses such as viral infections. Individuals with the severe infantile hepatocardiomuscular form of CPT II deficiency are at risk for liver failure, nervous system damage, coma, and sudden death.

The myopathic form is the least severe type of CPT II deficiency. This form is characterized by recurrent episodes of muscle pain (myalgia) and occasional weakness that is associated with the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin. This excess myoglobin may cause urine to be red or brown (myoglobinuria). Episodes of myalgia and rhabdomyolysis may be triggered by exercise, stress, exposure to extreme temperatures, infections, or fasting. The first episode of myalgia usually occurs during childhood or adolescence. The severity and frequency of episodes varies among affected individuals. Most people with the myopathic form of CPT II deficiency have no signs or symptoms of the disorder between episodes.

People with CPT II deficiency are often encouraged to avoid triggers such as long periods of fasting and intensive exercise to limit the occurrence of serious health problems.

CPT II deficiency is often detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. In individuals with CPT II deficiency, the blood levels of certain fats are elevated.

Frequency

CPT II deficiency is a rare disorder. The lethal neonatal form has been described in at least 20 families, while the severe infantile hepatocardiomuscular form has been identified in approximately 30 families. The myopathic form is the most common form, with more than 300 reported cases.

Causes

Variants (also called mutations) in the CPT2 gene cause CPT II deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 2.

This enzyme is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. During periods of fasting, fats are an important energy source for the liver and other tissues. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers. Before they can enter mitochondria, groups of fats called long-chain fatty acids must first be attached to a compound called carnitine. Once these fatty acids are inside mitochondria, carnitine palmitoyltransferase 2 removes the carnitine and prepares them for fatty acid oxidation.

Mitochondria. Credit: U.S. National Library of Medicine.

Variants in the CPT2 gene reduce the activity of carnitine palmitoyltransferase 2. As a result, there are not enough enzymes available to remove carnitine from long-chain fatty acids. With carnitine still attached, these fatty acids (known as long-chain acylcarnitines) cannot be broken down and used for energy. Reduced energy production can lead to some of the features of CPT II deficiency, such as hypoketotic hypoglycemia, myalgia, and muscle weakness. Long-chain acylcarnitines, which are detected in newborn screening tests, may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of CPT II deficiency.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. Rarely, people with only one variant in the CPT2 gene (known as carriers) have shown symptoms of the myopathic form of CPT II deficiency after strenuous activity, such as running long distances. More research is needed to determine how frequently carriers of CPT2 gene variants have health problems and under what circumstances.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• Carnitine palmitoyltransferase 2 deficiency
• CPT II deficiency
• CPT2 deficiency

Where this page came from

This page was imported from MedlinePlus Genetics, National Library of Medicine. Courtesy of MedlinePlus from the National Library of Medicine; its genetics summaries and the illustrations credited to the library are in the public domain. Pictures credited to others are not copied.

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