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  • Updated 03.22.2024
  • Released 03.30.1995
  • Expires For CME 03.22.2027

Carnitine palmitoyltransferase II deficiency



Carnitine palmitoyltransferase II deficiency is the most frequent hereditary disorder of fatty acid metabolism affecting muscle. The clinical hallmark of the muscle form are exercise-induced attacks of rhabdomyolysis. Less frequently, a severe infantile form with liver failure and hypoketotic hypoglycemia occurs. The author summarizes the clinical features of the disease and the search for an effective treatment that is still lacking.

Key points

• Carnitine palmitoyltransferase II deficiency frequently manifests with episodes of rhabdomyolysis after prolonged exercise and fasting leading to myoglobinuria and myalgia.

• This muscle form of the disease is the most frequent cause of hereditary myoglobinuria.

• A severe infantile form with liver failure and hypoketotic hypoglycemia and a lethal neonatal form represent other rarer manifestations.

• Analysis of acylcarnitine profile in blood by tandem mass spectrometry that is used in newborn screening is helpful to identify patients in later life.

• High intake of carbohydrate is recommended before exercise to prevent episodes of rhabdomyolysis.

Historical note and terminology

Carnitine palmitoyltransferase II deficiency is an inherited disorder of lipid metabolism affecting the entry of long-chain fatty acids into mitochondria. It was the first enzyme defect of fatty-acid oxidation to be discovered. In 1973, DiMauro and Melis-DiMauro described this enzyme defect in two brothers suffering from recurrent episodes of muscle pain and pigmenturia with occasional renal failure. The recurrent attacks were triggered by prolonged exercise, especially when the patient fasted (15). Several hundred patients have since been reported worldwide, and it has been clearly established that the defective enzyme is carnitine palmitoyltransferase II, the inner mitochondrial membrane component of the carnitine palmitoyltransferase system. Deficiency of the outer mitochondrial membrane component of the system, carnitine palmitoyltransferase I, was discovered in 1981 in a young girl with a pure "hepatic" presentation characterized by morning seizures due to fasting hypoglycemia (09).

Although exercise-induced recurrent myoglobinuria remains the most common manifestation of carnitine palmitoyltransferase II deficiency, other multisystemic phenotypes have been ascribed to a defect of this enzyme. Severe or lethal early-onset forms have been reported in neonates (30) and children (10) who present with hypoketotic hypoglycemia, liver failure, cardiomyopathy, generalized steatosis, developmental abnormalities, and early death.

In 1991 the human carnitine palmitoyltransferase II cDNA was cloned (25), and 1 year later, the first mutation in a patient with carnitine palmitoyltransferase II deficiency was identified (59).

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