Metabolic causes of rhabdomyolysis - CPT2 deficiency

Description

Carnitine palmitoyltransferase II (CPT2) deficiency - the most common inherited disorder of long-chain fatty acid oxidation causing recurrent exertional rhabdomyolysis, from impaired transport of long-chain fatty acids into the mitochondrial matrix for beta-oxidation

The adult-onset (myopathic) form is the most common CPT2 deficiency phenotype and the most common cause of hereditary recurrent rhabdomyolysis overall - presenting with episodic muscle pain/weakness triggered by prolonged exercise, fasting, cold exposure, or intercurrent illness, rather than the more severe infantile/neonatal forms

CPT2 is required for long-chain fatty acyl-carnitine to cross the inner mitochondrial membrane before beta-oxidation - deficiency means muscle cannot switch to fat oxidation for energy during prolonged exercise or fasting (when glycogen stores are depleted), causing an energy crisis and muscle breakdown specifically under these triggering conditions

Classic triggers: prolonged (not brief/high-intensity) exercise, fasting, cold exposure, febrile illness - distinguishing it from glycogen storage disease-related rhabdomyolysis (e.g. McArdle disease), which is triggered by brief, high-intensity exercise instead
Elevated CK during/after an episode (often markedly), with normal CK between episodes in many patients; acylcarnitine profile (elevated long-chain acylcarnitines) is a key diagnostic clue; genetic testing (CPT2 gene) confirms diagnosis

Avoid prolonged fasting and sustained endurance exercise; ensure adequate carbohydrate intake before prolonged exertion (providing an alternative fuel source to reduce reliance on fatty acid oxidation)
During an acute rhabdomyolysis episode: aggressive IV fluid hydration to prevent myoglobin-induced acute kidney injury, monitor renal function and electrolytes (particularly potassium)
A medium-chain triglyceride-enriched diet (bypassing the CPT2-dependent long-chain pathway, since medium-chain fatty acids enter mitochondria independently) can help some patients tolerate exercise better

Acute kidney injury (from myoglobinuria), malignant hyperthermia-like presentations under general anaesthesia (a recognised anaesthetic risk in undiagnosed patients), other fatty acid oxidation disorders

Recognising the specific exercise/fasting trigger pattern (prolonged, not brief exertion) is the key clinical clue distinguishing CPT2 deficiency from glycogen storage disease causes of exertional rhabdomyolysis, and guides both diagnosis and the specific lifestyle modification advice given

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