How does McArdle disease affect the breakdown of glycogen in muscles?

McArdle disease, also known as glycogen storage disease type V, is a rare hereditary condition characterized by a deficiency of the enzyme glycogen phosphorylase in muscle cells.12

Normally, this enzyme is responsible for catalyzing the breakdown of glycogen into simple sugars to provide the energy required for physical activity. In individuals with McArdle disease, mutations in the PYGM gene result in a nonfunctional or less functional form of the enzyme myophosphorylase. Consequently, muscle cells are unable to effectively perform glycogenolysis, preventing the muscles from accessing their stored energy reserves during exercise.12

Because the muscles cannot break down their own glycogen, muscle activity becomes entirely dependent on glucose and other nutrients circulating in the blood. This limitation typically leads to symptoms such as muscle pain, cramping, and, in severe cases, rhabdomyolysis following physical exertion.1