A young male presents complaining of an inability to perform strenuous exercise without bringing on painful muscle cramps and weakness. When he was administered an ischemic exercise test, his serum lactate concentrations did not increase significantly. A deficiency in which of the following enzymes is most likely the cause of the patient's muscle cramps?
Although a deficiency in a number of enzymes can result in exercise intolerance, the lack of an increase in serum lactate following ischemic exercise points to an inability to a defect in the breakdown of glycogen in the muscle. The muscle depends on glycogenolysis for intense exercise, and fatigue rapidly ensues when glycogen is depleted. Patients with a deficiency in the muscle isoform of glycogen phosphorylase (McArdle disease) can tolerate mild to moderate exercise, but get muscle cramps with strenuous exercise as a consequence of the lack of glycogenolysis in the muscle cell. Type V glycogen storage disease is an autosomal recessive disorder caused by deficiency of muscle glycogen phosphorylase. McArdle disease is a prototypical muscle energy disorder as the enzyme deficiency limits ATP generation by glycogenolysis and results in glycogen accumulation. Ref: Kishnani P.S., Chen Y. (2012). Chapter 362. Glycogen Storage Diseases and Other Inherited Disorders of Carbohydrate Metabolism. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e.
Glycogen phosphorylase
Carnitine palmitoyl transferase II
Glucose-6-phosphatase
Glycogen synthase