McArdle Disease (Glycogen Storage Disease Type 5)

McArdle disease, also known as glycogen storage disorder (GSD) type 5, is a rare inherited metabolic disorder primarily affecting skeletal muscles. This condition arises from a deficiency or complete lack of the enzyme muscle glycogen phosphorylase (myophosphorylase), essential for breaking down glycogen into glucose, the primary energy fuel for muscle cells. The disease follows an autosomal recessive inheritance pattern, meaning both gene copies must be mutated for the condition to manifest. In McArdle disease, the absence of myophosphorylase leads to the accumulation of glycogen in muscle tissues, as it cannot be adequately broken down to release glucose. Although glycolysis—the process of converting glucose to energy—is impaired, it is not completely blocked. Muscle fibers can still metabolize glucose to glucose-6-phosphate (G6P) downstream of the metabolic block, allowing partial energy production. This incomplete disruption leads to characteristic clinical symptoms, ranging from exercise intolerance, muscle cramps, and fatigue to more severe complications, eg, rhabdomyolysis, which is muscle breakdown during strenuous activities. Most patients with GSDs present in childhood; however, McArdle disease is one of those that have adult-onset forms as well. Unfortunately, treatment options are few and far between, although diet therapy has been observed to be efficacious in reducing clinical manifestations. McArdle disease was first reported in 1951 by Dr. Brian McArdle from London. This was after a patient with myalgia failed to show increased blood lactate levels during exercise. In 1959, it was described that the enzyme responsible for the affected step was myophosphorylase. The underlying gene for myophosphorylase () was first discovered in 1984.