What is CPT2 (carnitine palmitoyltransferase 2) deficiency?

Carnitine Palmitoyltransferase II (CPT2) Deficiency

CPT2 deficiency is an autosomal recessive inherited disorder of fatty acid oxidation that prevents long-chain fatty acids from being transported into the mitochondria for energy production, leading to potentially life-threatening episodes of metabolic decompensation. 1

Clinical Presentation

CPT2 deficiency presents in three distinct forms:

• Adult form: Most common presentation characterized by:

  • Episodes of rhabdomyolysis triggered by prolonged exercise 2
  • Muscle pain and weakness during attacks 3
  • Elevated creatine kinase levels (can reach >100,000 IU/L) 4
  • Acute kidney injury may occur due to myoglobinuria 3

• Infantile form: More severe presentation with:

  • Severe attacks of hypoketotic hypoglycemia 2
  • Cardiac damage that may lead to sudden death before 1 year of age 2
  • Liver dysfunction 1

• Neonatal form: Most severe and typically fatal presentation with:

  • Refractory cardiac arrhythmias 5
  • Acute multiorgan failure (hepatic, renal, muscular) 5
  • Brain and kidney dysorganogenesis 2
  • Usually lethal within the first month of life 2, 5

Pathophysiology

• CPT2 is located on the inner mitochondrial membrane 6
• The enzyme is responsible for converting long-chain acylcarnitines back to acyl-CoA inside the mitochondria 6
• Deficiency leads to accumulation of toxic long-chain acylcarnitines in various organs 5
• Inability to utilize fatty acids for energy production during periods of fasting or increased energy demands 1

Diagnosis

The diagnosis of CPT2 deficiency involves:

• Acylcarnitine profile analysis: Key diagnostic test showing characteristic patterns 1

  • Typically shows elevated long-chain acylcarnitines (C16, C18) 5
  • Low levels of C2 acylcarnitine may be present 5

• Additional laboratory tests:

  • Plasma carnitine levels (free and total) 1
  • Urine organic acids (usually normal in CPT2 deficiency) 1
  • Liver function tests (may be abnormal in symptomatic patients) 1
  • Creatine phosphokinase (elevated during acute episodes) 5

• Genetic testing:

  • Molecular analysis of the CPT2 gene for confirmation 5
  • The S113L mutation is found in approximately 50% of mutant alleles in the adult form 2
  • Over 40 different mutations have been identified 6, 2

• Important diagnostic caveat: Acylcarnitine profile may be normal between acute attacks, requiring molecular genetic testing when clinical suspicion is high 3

Management

Treatment strategies include:

• Dietary modifications:

  • Avoidance of fasting 6, 2
  • Low-fat diet enriched with medium-chain triglycerides 6, 2
  • Carnitine supplementation (particularly in severe forms) 2

• Lifestyle modifications:

  • Avoidance of prolonged exercise (for adult form) 6, 2
  • Ensuring adequate caloric intake during illness 1

• Medication:

  • Bezafibrate has shown symptomatic relief in some patients 4

• Genetic counseling:

  • Prenatal diagnosis can be offered for pregnancies at 25% risk of infantile/severe-type CPT2 deficiency 6, 2

Prognosis

• Adult form: Generally good with appropriate management 2
• Infantile form: Guarded prognosis with risk of sudden death 2
• Neonatal form: Poor prognosis with early mortality 2, 5