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 \ub7 kg\u961 \ub7 min\u961. 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