Pathophysiology of exercise performance in muscle disease.

Diseases of skeletal muscles (myopathies) produce two major patterns of exercise intolerance. In muscular dystrophies, there is a progressive loss of muscle fibers which results in increasing muscle weakness and reduced VO2max due to the loss of functional muscle mass. In disorders of muscle energy metabolism, muscle bulk and resting strength are preserved, but an imbalance in muscle energy production and utilization in exercise results in exertional muscle pain, cramping, weakness, or fatigue. Isometric exercise is impaired by disorders of anaerobic glycolysis. Dynamic exercise is limited by disorders of oxidative metabolism. Maximal oxygen uptake is low in mitochondrial myopathies which affect pyruvate oxidation and electron transport and in glycolytic disorders which limit the availability of carbohydrate for oxidation during high-intensity exercise. In carnitine palmityl transferase deficiency (under non-fasting conditions) VO2max is normal. Excessive cardiopulmonary responses to exercise occur in some mitochondrial myopathies and in myophosphorylase deficiency and may contribute to exercise intolerance in these diseases.