McArdle's disease. The unsolved mystery of the reappearing enzyme.

We assessed the frequency of muscle fibers showing histochemical phosphorylase activity in 27 muscle biopsies from 25 unrelated patients with McArdle's disease and studied by immunohistochemistry and in situ hybridization whether the muscle-specific isoform was expressed. Positive phosphorylase fibers were observed in 19% of our series of biopsies. We show that the enzyme isoform expressed in regenerating fibers differs according to the genotype of patients: the muscle-specific isoform is transcribed and translated in patients with none of the described mutations in at least one allele of the myophosphorylase gene, whereas it is neither transcribed nor translated in patients with identified mutations in both alleles.