Phosphorylase deficiency McArdle

Phosphorylase deficiency (McArdle s disease, glycogenosis type V) is an autosomal recessive myopathy caused by a genetic defect of the muscle isoenzyme of glycogen phosphorylase (Fig. 42-1). Intolerance of strenuous exercise is present from childhood, but usually onset is in adolescence, with cramps after exercise [1, 5]. Myoglobinuria occurs in about one-half of patients. If they avoid intense exercise, most patients can live normal lives however, about one-third of them develop some degree of fixed weakness, usually as a late-onset manifestation of the disease. In a few patients, weakness rather than exercise-related cramps and myoglobinuria characterizes the clinical picture. 

TypeV Myophosphorylase deficiency, McArdle s syndrome Absence of muscle phosphorylase Diminished exercise tolerance muscles have abnormally high glycogen content (2.5-4.1%). Little or no lactate in blood after exercise. 

Glycogen phosphorylase deficiency in muscle gives rise to muscle weakness, frequent cramp and ease of fatigue (McArdle s syndrome). It also gives rise to hypoglycae-mia if the liver enzyme is deficient (Chapter 6). 

D-1) Muscle phosphorylase deficiency (Type V GSD McArdle s Disease). Liver phosphorylase is normal, but muscle phosphorylase is deficient. The patient cannot break down muscle glycogen and experiences muscle cramps and weakness with exercise. Muscle biopsy may confirm the enzyme defect. There is no significant rise in lactate in an ischemic exercise test. Magnetic resonance spectroscopy may be useful in diagnosing changes in muscle metabolic function. 

The answer is c. (Murray, pp 199-207. Scriver, pp 1521-1552. Sack, pp 121-138. Wilson, pp 287-317.) Muscle phosphorylase deficiency leads to a glycogen storage disease [McArdles disease (232600)] and, in young adults, an inability to do strenuous physical work because of muscular cramps resulting from ischemia. The compromised phosphorylation of muscle glycogen characteristic of McArdle s disease compels the muscles to rely on auxiliary energy sources such as free fatty acids and ambient glu-... 

Bartram, C., Edwards, R. H. T., and Beynon, R. J. (199S). McArdle s disease Muscle glycogen phosphorylase deficiency. Biochim. Biophys. Acta 1272, 1-13. 

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

The normed muscle concentration of pyridoxal phosphate is of the order of 10 nmol per g in patients with McArdle s disease (glycogen storage disease from congenital lack of glycogen phosphorylase), the muscle content of pyridoxal phosphate is reduced to one-fifth of this. There is some evidence that patients with McArdle s disease show signs of vitamin Be deficiency, su esting that the muscle pool of the vitamin is important in maintenance of vitamin Be homeostasis (Beynon et ed., 1995). 

A. Glycogen accumulates because muscle phosphorylase is deficient in McArdle s disease (a glycogen storage disease). 

Rgure 26.5 GSD V, McArdle s disease. GSD V (autosomal recessive) is caused by a deficiency of the muscle form of phosphorylase (myophosphorylase). Consequently, GSD V patients are unable to mobilise glycogen for energy metabolism, which results in fatigue, muscle peiin and myoglobinuria following exercise. 

---