The 'McArdle paradox': Exercise is a good advice for the exercise intolerant

Abstract

McArdle disease (glycogen storage disease type V, OMIM database number 232600) may provide the ultimate model of exercise intolerance in humans, and thus is of great interest in the sports medicine setting. The condition is an autosomal recessive disorder of muscle glycogen metabolism originally described in 1951 by Brian McArdle.1 Patients have pathogenic mutations in both alleles of the PYGM gene, which encodes myophosphorylase, the skeletal muscle isoform of glycogen phosphorylase.2 As a result, myophosphorylase activity is totally absent. Because this enzyme initiates the breakdown of muscle glycogen leading to liberation of glucose-1-phosphate, patients are unable to obtain energy from their muscle glycogen stores. Hence this disease is arguably the paradigm of exercise intolerance in humans.2 Exercise is the trigger for symptom occurrence in McArdle patients; as such, they tend to be averse to exercise and have often been advised by clinicians to refrain from exercise.