Research on molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). Use of new protein mapping and immunological techniques.

McArdle's disease is due to the lack of activity of muscle glycogen phosphorylase. We investigated the presence of an inactive protein by two techniques: (a) Bidimensional protein maps, using a modification of the original O'Farrell technique allowing location of phosphorylase. (b) Purification of enzyme from crude muscle extracts, using an immunoaffinity microchromatographic procedure. Protein maps of three patients were obtained. No protein was detected at the normal (97 K) position of phosphorylase but 70 and 60 K spots were visible. Results of enzyme purificaton by immunoaffinity were negative for one patient, whereas a small band of phosphorylase-like material was detected in the other. Our results confirm the molecular heterogeneity of the disease. We think such methods might be useful for investigating other genetic diseases.