Carnitine palmitoyltransferase II deficiency

Carnitine palmitoyltransferase II deficiency is a condition that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through the diet, is required by cells to process fats and produce energy. People with this disorder have a faulty enzyme that disrupts carnitine's role in processing long-chain fatty acids.

The three main types of carnitine palmitoyltransferase II deficiency are: a lethal neonatal form; a severe infantile form that affects the liver, heart, and muscles (hepatocardiomuscular form); and a less severe form that affects only the muscles (myopathic form). Infants with the lethal neonatal form of this disorder usually experience respiratory failure, liver failure, seizures, and an irregular heart beat (arrythmia) leading to cardiac arrest. In many cases, the brain and kidneys are also abnormal. Usually, affected infants do not survive their first year.

Signs and symptoms of the infantile hepatocardiomuscular type of this disorder usually appear between the ages of 6 and 24 months. This condition involves recurring episodes of low ketone levels. Ketones are products of fat breakdown that are used for energy. Low blood sugar (hypoglycemia) is another major feature of this condition. Together these signs are called hypoketotic hypoglycemia; they can cause a loss of consciousness or seizures. Liver failure and an enlarged liver (hepatomegaly) are also sometimes seen. In many cases, there is also heart involvement, which can result in sudden unexpected death during infancy. Episodes are often triggered by infections, fever, or fasting.

The myopathic form is the most frequent and typically the least severe form of carnitine palmitoyltransferase II deficiency. It has a variable age of onset and is characterized by recurrent episodes of muscle pain (myalgia) and weakness. This condition is sometimes associated with the abnormal breakdown of an oxygen-binding muscle protein called myoglobin (myoglobinuria) or the breakdown of muscle tissue (rhabdomyolysis). Rarely, myoglobinuria can result in kidney failure.

This disorder is rare. The lethal neonatal form of this disorder has been described in more than 10 families, while the severe infantile hepatocardiomuscular form has been identified in approximately 20 families. More than 200 cases of the myopathic form have been reported.

Mutations in the CPT2 gene cause carnitine palmitoyltransferase II deficiency.

Mutations in the CPT2 gene lead to the production of a defective version of an enzyme called carnitine palmitoyltransferase II. Together with carnitine, this enzyme helps release long-chain fatty acids from a particular transport enzyme. If carnitine palmitoyltransferase II is defective, long-chain fatty acids from food and fats stored in the body cannot be broken down and processed. As a result, these fatty acids are not converted into energy, which can lead to characteristic signs and symptoms of this disorder, such as myalgia, weakness, and hypoglycemia. Excess long-chain fatty acids may build up in tissues, damaging the heart, liver, and muscles and causing more serious complications.

Read more about the CPT2 gene.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.