Why do patients with McArdle's disease have decreased exercise capacity?

Disorders of myoglycogenolysis, such as myophosphorylase deficiency(McArdle's disease), and myoglycolysis, such as phosphofructokinase deficiency (Tarui disease), are characterized by electrically silent, exercise-provoked contractions called "contractures," premature exertional fatigue and excessive cardiovascular responses to exercise.^1-3 McArdle's disease and Tarui disease as well as other disorders of myoglycolysis, such as phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, and lactate dehydrogenase deficiency, are important to neurology because these disorders allow us to explore the interactions between muscle metabolism and muscle contraction.¹ Beyond providing the power for movement, skeletal muscle is the largest protein store in the human body and is important in the regulation of glucose metabolism.⁴ The article by Haller et al.⁵ in this issue of Neurology focuses on physiologic alterations of skeletal muscle in McArdle's disease that contribute to exercise intolerance and exaggerated cardiovascular responses to exercise. Their work represents the collaboration of well-respected muscle physiologists from both sides of the Atlantic Ocean.

Contracture was initially thought to be similar to the rigor of rigor mortis. Ischemic exercise would deplete adenosine triphosphate (ATP) because the muscle fiber could not generate ATP through the glycolytic pathway under anaerobic conditions. Without …