CPT2

CPT2, or carnitine palmitoyltransferase 2, is a mitochondrial enzyme that plays a key role in the beta-oxidation of long-chain fatty acids. It catalyzes the conversion of acylcarnitine to acyl-CoA within the mitochondrial matrix, enabling fatty acids to enter the beta-oxidation pathway. CPT2 works in conjunction with CPT1, which forms acylcarnitines at the outer mitochondrial membrane, and with the carnitine-acylcarnitine translocase to shuttle substrates across membranes. The enzyme is primarily expressed in skeletal muscle and the heart, with lower activity in other tissues.

Mutations in the CPT2 gene cause CPT II deficiency, an autosomal recessive metabolic disorder with three main clinical forms. The most common is the adult myopathic form, characterized by recurrent episodes of exercise-induced muscle pain, stiffness, weakness, and myoglobinuria, often triggered by prolonged exertion, cold exposure, or fasting. The infantile and neonatal-onset forms are more severe and may include hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, and early mortality. Diagnosis is based on clinical presentation, elevated serum creatine kinase during attacks, characteristic acylcarnitine profiles (elevated long-chain species), and confirmatory genetic testing for CPT2 mutations.

Management emphasizes avoidance of fasting and triggers, a diet reduced in long-chain fats and often enriched with carbohydrates and medium-chain triglycerides, and prompt treatment of acute episodes with hydration and glucose. Some patients may receive L-carnitine supplementation, though evidence for its benefit varies. Ongoing research aims to define genotype–phenotype correlations and explore targeted therapies.