Metabolic causes of rhabdomyolysis - McArdle disease

Description

McArdle disease (glycogen storage disease type V) - myophosphorylase deficiency, impairing muscle glycogen breakdown and causing exercise intolerance with brief, high-intensity exertion specifically (in contrast to the prolonged-exertion trigger pattern of fatty acid oxidation disorders)

One of the more common glycogen storage diseases causing exercise-related myopathy; autosomal recessive inheritance

Myophosphorylase is required to mobilise stored muscle glycogen for rapid ATP generation during high-intensity anaerobic exercise - deficiency means muscle cannot access this glycogen reserve, causing early fatigue, cramping, and potential rhabdomyolysis specifically during the first few minutes of intense exertion, before aerobic fatty acid/oxidative metabolism can take over

The classic "second wind" phenomenon - symptoms improve if the patient slows down or rests briefly early in exercise, then can continue at a similar intensity, as the muscle shifts to using blood-borne glucose and free fatty acids (bypassing the defective glycogenolysis pathway) - a distinctive, diagnostically useful clinical feature
Forearm exercise test - classically shows a failure of the expected lactate rise (since glycolysis from muscle glycogen cannot proceed) with an exaggerated ammonia rise - though this test has largely been superseded by genetic testing given the risk of triggering a compartment syndrome-like reaction
Genetic testing (PYGM gene) is now the preferred diagnostic approach

Avoid brief, high-intensity/explosive exercise; low-intensity aerobic exercise is generally well tolerated and can even be therapeutic (improving overall exercise capacity over time)
Teaching patients to recognise and use the "second wind" phenomenon (brief rest/pacing at the start of exercise) allows continued physical activity more safely
Pre-exercise carbohydrate/sucrose loading has some evidence for improving exercise tolerance in this specific condition (providing blood glucose as an alternative fuel)
Manage acute rhabdomyolysis episodes as for any cause (hydration, renal monitoring)

Acute kidney injury from myoglobinuria, other glycogen storage diseases, CPT2 deficiency (the key differential given the opposite exercise-trigger pattern)

The exercise trigger pattern (brief/intense for McArdle vs prolonged/sustained for CPT2 deficiency) is the single most useful bedside clue distinguishing these two most common causes of hereditary exertional rhabdomyolysis, before genetic confirmation

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