Foundations · Year 1 · from Foundations
Case 3: Carnitine Palmitoyltransferase II (CPT-II) Deficiency
Clinical Image
Source: Wikipedia - Rhabdomyolysis - CC BY-SA 3.0
Case Presentation
A 25-year-old man presents to the emergency department with severe muscle pain and dark brown urine after completing a marathon. He reports this is his third episode of similar symptoms, with previous episodes occurring after prolonged exercise and once during a fasting religious observance. Physical examination reveals diffuse muscle tenderness. Urinalysis shows 3+ blood but no red blood cells on microscopy (myoglobinuria). Laboratory studies reveal CK 85,000 U/L (markedly elevated), creatinine 2.4 mg/dL (acute kidney injury from myoglobin nephrotoxicity), and elevated transaminases. He is diagnosed with rhabdomyolysis. Given his recurrent episodes triggered by prolonged exercise and fasting, a metabolic myopathy is suspected. Acylcarnitine profile shows elevated long-chain acylcarnitines. Genetic testing confirms compound heterozygous mutations in CPT2, consistent with the adult myopathic form of CPT-II deficiency. The carnitine shuttle is essential for transporting long-chain fatty acids into mitochondria; during prolonged exercise when fatty acids become the primary fuel, impaired import leads to energy failure and muscle breakdown. He is counseled on avoiding prolonged exercise, maintaining carbohydrate intake during physical activity, and pre-treatment hydration strategies.
Key Learning Points
- CPT-II deficiency impairs transport of long-chain fatty acids into mitochondria via the carnitine shuttle; the adult myopathic form causes recurrent rhabdomyolysis triggered by prolonged exercise, fasting, cold, or infection
- During sustained exercise, muscles increasingly rely on fatty acid oxidation; when this is impaired, ATP depletion causes muscle breakdown (rhabdomyolysis) with release of myoglobin and CK
- Myoglobinuria can cause acute kidney injury through tubular obstruction and direct nephrotoxicity; treatment includes aggressive IV fluid resuscitation to maintain urine output