Glycogenosis type V. McArdle disease. Myophosphorylase deficiency.
Incidence
1:50,000 births. AR inheritance, with occasional dominant transmission. Gene coded in chromosome 11. Recent molecular studies have identified 10 mutations in the myophosphorylase gene.
Clinical Characteristics
Sx. start usually after age 5 years. There is muscle cramps & pain after first minutes of exercise, often with myoglobinuria. Most children decrease their activity. They may have a 'second wind' phenomenon when they restart activity (switch glucose metabolism to fat). Permanent weakness may be observed late. Atrophy also. Some pts. have a slow progressive myopathy without cramps. It is a muscle disease. Repeated episodes of myoglobinuria may produce chronic renal impairment. Recent molecular studies have identified 10 mutations in the myophosphorylase gene. One of these, a nonsense mutation at codon 49 is found in more than 75% of patients, whereas approximately 10% of patients have a mutation at codon 204.
Precipitants
Exercise produce muscle cramps and pain after first few minutes of exercise.
Provocation Tests
Ischaemic exercise test: Lactate should increase higher than 2 mmol/L with exercise normally. In this condition, there is no increase of lactate, and cramps may appear during the test.
Diagnostic Procedures
EB-muscle. Muscle biopsy shows moderate increase of subsarcolemmic glycogen. High CPK in 90% of pts. Mutations have been identified in this condition. These can now be detected in DNA isolated from the blood. This analysis provides a practical alternative to muscle biopsy for initial screening.