McArdle’s DiseaseDz

Last updated: January 18, 2024

Synonyms: Myophosphorylase deficiency

ICD-9 Code: 271.0.

ICD-10 Code: E74.0

Definition: Inherited disorder of glycogen metabolism with a deficiency of myophosphorylase that impairs glycogen breakdown for energy utilization by muscle.

Pathogenesis: McArdle disease is caused by a deficiency of myophosphorylase and is a good example of a glycolytic disorder. Myophosphorylase deficiency impairs the ability of the muscle to metabolize glycogen as an energy source. This is particularly important during anaerobic muscle activity, when oxidative phosphorylation cannot be depended on because of reduced oxygen delivery to the muscle tissue.

Pathology: Absence of myophosphorylase activity on muscle biopsy.

Demographics: Typically is diagnosed early in life but occasionally is seen in neonates or goes unnoticed until adulthood.

Cardinal Findings: Primarily manifests as episodic, exercise-induced muscle pain, fatigue, cramps, and weakness, and symptoms are relieved by rest and often result in myoglobinuria. Some patients will experience fewer symptoms by ingesting glucose or fructose before exercise. Many patients describe a “second wind” phenomenon wherein after exercise and symptom onset, patients stop exercising briefly, only to restart exercise and then perform better. This represents a transition from glycolytic-dependent pathway to oxidative phosphorylation and release of glucose and free fatty acids as energy sources.

Uncommon Findings: Over time, some patients will develop chronic fixed proximal muscle weakness. McArdle’s disease may cause rhabdomyolysis, thereby causing acute tubular necrosis and renal dysfunction. Gout and hyperuricemia may occur in patients with McArdle’s disease.

Diagnostic Tests: The majority of patients have low-level muscle enzyme (CPK, aldolase) elevations in response to low-level physical activity. However, with exercise, these may increase 10-fold or more and result in myoglobinuria. Myoglobinuria and higher levels of muscle enzyme elevations should lead one to suspect rhabdomyolysis. Patients should undergo ischemic (or nonischemic) forearm exercise testing. Patients with McArdle disease demonstrate an inability to raise serum lactate levels in the exercised arm, whereas serum ammonia (and sometimes creatine phosphokinase) levels will rise. Myophosphorylase staining of the muscle tissue will confirm the diagnosis.

Keys to Diagnosis: Exercise-induced myalgia or cramping with a resultant myoglobinuria and increase in creatine phosphokinase. Diagnosis is confirmed by a lack of myophosphorylase activity on muscle biopsy or the inability to generate lactate with ischemic forearm exercise testing.

Differential Diagnosis: McArdle’s disease needs to be differentiated from inflammatory myositis, and other causes of myopathy including include myoadenylate deaminase deficiency, carnitine palmityl transferase deficiency (only after prolonged exercise), acid maltase deficiency (with early, severe respiratory involvement), and mitochondrial myopathies.

Therapy: Currently, no effective treatment is available for McArdle’s disease, but accurate diagnosis is important to appropriately counsel patients regarding the need for prompt treatment of episodes of myoglobinuria. Creatinine-enriched dietary supplementation has been advocated by some.

McArdle B. Myopathy due to defect in muscle glycogen breakdown. Clin Sci 1951;10:13–33. PMID: 24540673 
Wolfe GI, Baker NS, Haller RG, et al. McArdle’s disease presenting with asymmetric, late-on-set arm weakness. Muscle Nerve 2000;23:641–645. PMID: 10716777

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