A metabolic myopathy due to absence of muscle phosphorylase

Abstract

Detailed functional and metabolic studies have been conducted in a nineteen year old boy who had a lifelong history of progressive weakness upon usage of exercised muscles and severe cramps if exertion was intense or prolonged. There was no muscular wasting, and strength during initial exercise was normal. The family history was non-contributory. Basal serum lactic and pyruvic acid levels were normal. However, there was no rise following treadmill exercise, in contrast to a transitory but significant rise in controls. Ischemic exercise of the forearm muscles was poorly maintained, and no elevation of lactic or pyruvic acid was noted in the venous return from the arm in contrast to a fourfold increase in control subjects. In the basal state, treadmill exercise at 4 miles per hour (10 degree incline) was limited to about four minutes. Improvement in treadmill exercise tolerance was marked following continuous intravenous infusion of glucose, fructose or lactate but there was no effect from galactose or glycerol. Epinephrine infusion produced a normal hyperglycemic response. Biochemical and histochemical analyses of thigh muscle revealed a fourfold increase in stored glycogen in the muscle and no reliably detectable phosphorylase. Glycolysis in a tissue homogenate, as indicated by lactate production, was markedly reduced. It was raised to near normal intensity by the addition of glucose-1-phosphate or glucose-6-phosphate. The uridine diphosphate glucose pathway for glycogen synthesis was found to be intact. This disorder, originally described by McArdle in 1951, is very rare. The deficiency in phosphorylase appears to be confined solely to the skeletal musculature. Because of the increase in stored muscle glycogen the disorder may be classified as another form of glycogen storage disease.