Novel mutation in the PYGM gene resulting in McArdle disease

Background: McArdle disease is a common metabolic disorder characterized by marked exercise intolerance, premature fatigue during exertion, myalgia, and cramps. Despite the wide knowledge of the molecular basis of McArdle disease, few studies have used a physiological approach or explored the possibility of improving the exercise capacity of these patients. Objectives: To describe 3 unrelated patients with McArdle disease with a novel mutation in the PYGM gene and to assess the physical capacity in 1 of them. Design: Using molecular genetic approaches, we identified the underlying molecular defect in 3 patients with McArdle disease. Physical performance was evaluated in 1 patient by means of an exercise tolerance test on a bicycle ergometer. Setting: Two university hospitals. Exercise physiology studies were performed in a university department. Patients: The 3 patients showed common features of McArdle disease. They were definitively diagnosed by histochemistry, biochemistry, or molecular genetic analysis. Results: All of the 3 patients were genetic compounds for the common Arg50Stop mutation and a novel c. 13_14delCT mutation in the PYGM gene. The peak oxygen uptake (VO2peak) of the patient who performed the exercise test was only 20.2 mL center dot kg(-1) center dot min(-1). Conclusions: Together with the novel mutation, there is a markedly decreased exercise capacity in a patient with McArdle disease, which could account for the profound alteration in the capacity for performing normal activities of daily living in this subpopulation.