Why do people with McArdle disease experience muscle cramps during exercise?

People with McArdle disease experience muscle cramps during exercise because their muscle cells lack the enzyme glycogen phosphorylase, which is essential for breaking down stored glycogen into the simple sugars required for energy production.1

Normally, skeletal muscle contraction relies on the synthesis of adenosine triphosphate (ATP) through the breakdown of glycogen via glycolysis. Because individuals with this metabolic disease cannot access these internal glycogen reserves, their muscles become solely dependent on glucose and other nutrients circulating in the blood. When the demand for energy during physical activity exceeds what can be supplied by the blood, the resulting energy deficit manifests as pain and cramping. These symptoms typically subside with rest, though excessive exertion can lead to rhabdomyolysis, a dangerous condition involving muscle tissue breakdown.21