Glycogen phosphorylase storage disease

Lederer B, Van Hoof F, Van den Berghe G, Hers HG (1975) Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen storage disease. A study of phosphorylase kinase deficiency. Biochem J 147 23-35... 

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). 

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-... 

Several types of glycogen-storage disease are now known in most cases, the accumulation of glycogen can be correlated with a relative deficiency of either n-glucose 6-phosphatase or the debranching-enzyme system (Type I and III disease, respectively). In a very few cases, the enzymic defect is either in branching enzyme or in phosphorylase (Type IV or VI disease, respectively) see Table VII. In the Type II and V diseases, the enzyme deficiencies are different from the above, but have not yet been fully identified. 

In the Type VI diseases, there appears to be abnormally low or complete absence of phosphorylase activity. In three cases (Type Via) examined by Hers, the activity of the liver phosphorylase was about 5 units, compared with values of 12-33 units for other cases of glycogen-storage disease, although the muscle phosphorylase activity was normal. 

In McArdle disease (type V glycogen storage disease) the first patient was a yoimg man who was weak and developed severe muscle pain on doing modest exercise. Biopsy of his muscle showed accumulation of glycogen, and enzyme assays revealed low glycogen phosphorylase activity. Predict the effect of exercise on the lactate concentration in such a patient. 

Myopathic glycogenoses Glycogen storage disease type V Muscle phosphorylase PYGM McArdle disease... 

Another form of glycogen storage disease with low phosphorylase activity was described by Hers and his associates. In this patient, the simple addition of phosphorylase B kinase to the liver homogenates restored phosphorylase activity to normal. Therefore, it was established in that case that the low phosphorylase activity resulted not from a decrease in the molecular concentration of active phosphorylase or a molecular alteration of phosphorylase, but from a lack of phosphorylase kinase. The conversion of active to inactive phosphorylase is illustrated in Fig. 3-13. 

---