McArdle Disease
McArdle disease is an autosomal recessive neuromuscular disease that is characterized by the absence of muscle glycogen phosphorylase resulting in impaired muscle metabolism. Glycogen phosphorylase is a key enzyme that takes part in the first step of glycogenolysis. Misdiagnoses are common even through adult years.
Clinical Features
Patients experience episodes of muscle pain, exercise intolerance, and tachycardia at the beginning of any physical activity and during strenuous activity, isometric muscle contraction, and/or resistance training. In infants, symptoms may include difficulty crawling more than a few yards, while toddlers may want to be carried or put in a push-chair all the time and complain of pain when walking. In children, the disease can lead to an inability to run more than 100 meters, an inability to keep up with peers, and collapse or vomiting during sporting activities.
One hallmark of McArdle disease is the "second wind" phenomenon. During aerobic activity, patients experience a period where symptoms improve after 8-10 minutes of exercise. This is thought to be due to the switch from glycogen to fat as the primary energy source during exercise.
However, severe episodes of muscle contracture can lead to rhabdomyolysis/myoglobinuria. This can cause muscle swelling and pain, discolouration of urine, collapse, and acute renal failure. Creatine kinase (CK) levels are markedly raised during these episodes, with levels between 40,000–250,000 IU/L.
Diagnosis
Diagnosis of McArdle disease involves a combination of clinical presentation, laboratory tests, and genetic testing. Baseline serum CK is usually raised (10-15 times the normal range), while serum urate is frequently elevated. A non-ischemic forearm exercise test shows no significant rise in lactate, while DNA analysis can identify common mutations in Northern Europeans, such as p.Arg50X and p.Gly205Ser. Next-tier testing involves full PYGM sequencing. Muscle biopsy is rarely required and shows vacuolar myopathy, sub-sarcolemmal glycogen deposition, and absent muscle glycogen phosphorylase activity.
Treatment
Treatment for McArdle disease is mainly supportive, with an emphasis on avoiding strenuous exercise and preventing muscle damage. Patients are encouraged to engage in regular low-intensity exercise, which can improve muscle function and reduce symptoms. Dietary interventions, such as a high-protein diet, can also help to minimize symptoms.
