The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic implications

J Inherit Metab Dis. 2015 Mar;38(2):221-30. doi: 10.1007/s10545-014-9743-2. Epub 2014 Jul 23.


Numerous biomedical advances have been made since Carl and Gerty Cori discovered the enzyme phosphorylase in the 1940s and the Scottish physician Brian McArdle reported in 1951 a previously 'undescribed disorder characterized by a gross failure of the breakdown in muscle of glycogen'. Today we know that this disorder, commonly known as 'McArdle disease', is caused by inherited deficiency of the muscle isoform of glycogen phosphorylase (GP). Here we review the main aspects of the 'pathogenomics' of this disease including, among others: the spectrum of mutations in the gene (PYGM) encoding muscle GP; the interplay between the different tissue GP isoforms in cellular cultures and in patients; what can we learn from naturally occurring and recently laboratory-generated animal models of the disease; and potential therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Exercise Tolerance
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Glycogen Phosphorylase, Muscle Form / deficiency
  • Glycogen Phosphorylase, Muscle Form / genetics*
  • Glycogen Storage Disease Type V / enzymology
  • Glycogen Storage Disease Type V / genetics*
  • Glycogen Storage Disease Type V / physiopathology
  • Glycogen Storage Disease Type V / therapy
  • Humans
  • Mice, Transgenic
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / physiopathology
  • Mutation*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis


  • Glycogen Phosphorylase, Muscle Form