Carnitine palmitoyltransferase II deficiency

Marcus Deschauer MD (Dr. Deschauer of Technical University of Munich received honorariums from Genzyme for consulting work and speaking engagements.)
Darryl De Vivo MD, editor. (Dr. De Vivo of Columbia University has no relevant financial relationships to disclose.)
Originally released March 30, 1995; last updated January 4, 2017; expires January 4, 2020

This article includes discussion of carnitine palmitoyltransferase II deficiency and CPT II deficiency. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Carnitine palmitoyltransferase II deficiency is the most frequent hereditary disorder of fatty acid metabolism affecting muscle. Exercise-induced attacks of rhabdomyolysis are the clinical hallmark. The author summarizes the clinical features of the disease and reviews the pilot studies on bezafibrate treatment that revealed conflicting results.

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 also 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. Abnormalities of lipid catabolism as possible causes of human disease were first suggested in the late 1960s by morphological observations of excessive accumulation of lipid droplets within muscle fibers (Bradley et al 1969). In 1973, carnitine palmitoyltransferase type II deficiency was the first enzyme defect of fatty-acid oxidation to be discovered. DiMauro and Melis-DiMauro described this enzyme defect in 2 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 (DiMauro and Melis-DiMauro 1973). More than 350 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 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 (Bougneres et al 1981).

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 (Hug et al 1991; Witt et al 1991) and children (Demaugre et al 1991) 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 (Finocchiaro et al 1991), and 1 year later, the first mutation in a patient with carnitine palmitoyltransferase II deficiency was identified (Taroni et al 1992a).

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