McArdle's disease

A condition caused by an inborn deficiency of muscle phosphorylase. There is an abnormal accumulation of glycogen in muscle tissue. Symptoms are exercise intolerance - muscular pain, fatigability - and muscle cramping. Rest relieves the muscle pain and enables exercise to resume. However, anaerobic activity leads to severe fixed contractures and myoglobinuria from muscle breakdown which can lead to acute renal failure. Size and initial power tone of muscle are normal at outset of exercise. Onset usually in early childhood, although diagnosis often not made until the second or third decade. Affected people appear normal on presentation with exercise intolerance but creatine kinase is raised. Many people experience a worsening of symptoms after middle age when muscle wasting may be seen. Unlike other types of glycogenosis the disease is not fatal and the missing enzyme does not impair the functioning of other body systems. Inheritance is autosomal recessive. Dominant form rarely reported.

McArdle in 1951 first described the condition in a male patient, 30 years of age, who experienced pain followed by weakness and stiffness after exercise as having been present "all his life", but doctors had dismissed his symptoms as hysterical.

On examination McArdle noted that, unlike ordinary cramps, those experienced by the patient were electrically silent, and that his venous lactate level failed to increase after ischaemic exercise. He realised that this was the same phenomenon that occurs when muscle is poisoned by iodoacetate, a substance that blocks the breakdown of glycogen into glucose and prevents the formation of lactic acid.

The enzyme deficiency was discovered in 1959 by W. F. H. M. Mommaerts et al.

The terms Cori's syndrome and Cori type V glycogenosis have been used as synonyms for McArdle's. Cori's disease is GSD Type 3 and has been entered as Forbes' disease, under Gilbert Burnett Forbes, Amerikan paediatrician, 1915-2003.

We thank Andrew Wakelin for information submitted.

• B. McArdle:
  Myopathy due to a defect in muscle glycogen breakdown.
  Clinical Science, London, 1951, 10: 13-33.
• R. Schmid, R. Mahler:
  Chronic progressive myopathy with myoglobinuria: demonstration of a glycogenolytic defect in the muscle.
  The Journal of Clinical Investigation, New York, 1959, 38: 2044-2058.
• R. Schmid, L. Hammaker:
  Hereditary absence of muscle phosphorylase (McArdle’s syndrome).
  New England Journal of Medicine, Boston, 1961, 264: 223-225.
• C. M. Pearson:
  A metabolic myopathy due to absence of muscle phosphorylase.
  American Journal of Medicine, New York, 1961, 30: 502-517.
• W. F. H. M. Mommaerts, Barbara Illingworth, Carl M. Pearson, R. J. Guillory,
  K. Seraydarian:
  A functional disorder of muscle associated with the absence of phosohorlylase.
  Proceedings of the National Academy of Sciences of the United States of America, Washington, 1959, 45: 791-797.