Skeletal Muscle, McArdle disease

McArdle disease is a glycogen storage disease (GSD type V) caused by inactivating mutations in the muscle-specific isoform of glycogen phosphorylase (myophosphorylase, PYGM, 11q13.1). This results in the inability to break down glycogen but McArdle disease is unique among GSDs in that it exclusively affects skeletal muscle. It is also one of the most common GSDs, although the prevalence is only 1 in 100,000. Patients typically present in childhood or adulthood with exercise intolerance, muscle pain, rhabdomyolysis, and a characteristic “second wind” phenomenon. Microscopically, muscle biopsy shows general myopathic features along with PAS-positive diastase-sensitive subsarcolemmal vacuoles that contain non-membrane bound glycogen on electron microscopy. Histochemistry for myophosphorylase shows absent enzyme activity but must be interpreted along with an appropriate positive control (checkerboard staining pattern). Treatment is generally supportive and with lifestyle changes.

See Related Content for PAS and PASD stains.