McArdle Disease and Exercise Physiology

Abstract

McArdle disease (glycogen storage disease Type V; MD) is a metabolic myopathy caused by a deficiency in muscle glycogen phosphorylase. Since muscle glycogen is an important fuel for muscle during exercise, this inborn error of metabolism provides a model for understanding the role of glycogen in muscle function and the compensatory adaptations that occur in response to impaired glycogenolysis. Patients with MD have exercise intolerance with symptoms including premature fatigue, myalgia, and/or muscle cramps. Despite this, MD patients are able to perform prolonged exercise as a result of the "second wind" phenomenon, owing to the improved delivery of extra-muscular fuels during exercise. The present review will cover what this disease can teach us about exercise physiology, and particularly focuses on the compensatory pathways for energy delivery to muscle in the absence of glycogenolysis.

Figure 1

Adenine nucleotide degradation. ATP, adenosine triphosphate; ADP, adenosine diphosphate; IMP, inosine monophosphate; NH3, ammonia.

Figure 2

Schematic of metabolic pathways in the skeletal muscle of patients with McArdle disease. The dotted line indicates impaired glycogenolysis. Previous studies by the Tarnopolsky group have demonstrated increased GLUT4, MCT1, and MtCK protein levels in McArdle disease (MD) patients [27,28] FABPm, plasma membrane-associated fatty acid binding protein; FATP, fatty acid transport protein; G-6-P, glucose 1-phosphate; MCT, monocarboxylate transporter; mtCK, mitochondrial creatine kinase