McArdle disease or Glycogen Storage Disease type V (GSD V; myophosphorylase deficiency; MIM 232600) its an inborn error of glycogen metabolism, caused by a deficiency in muscle specific isoform of glycogen phosphorylase. This metabolic myopathy is characterised by exercise intolerance, myalgia, cramps and episodic myoglobinuria, symptoms that usually appear during the second or third decade of life.
The diagnosis was typically made in muscle biopsy by histological analysis (demonstration of subsarcolemmal glycogen deposits and negative histochemical stain for phosphorylase) and/or measurement of muscle phosphorylase activity. Although since 1984, when the gene of muscle isoform of phosphorylase (myophosphorylase) was cloned and assigned to chromosome 11 (11q13), molecular genetics analysis has been more and more used to confirm the clinical diagnosis. Until now, 146 pathogenic mutations have been described (according to HGMDTM) including nonsense, missense and framshift mutations. High genetic heterogeneity is a hallmark of McArdle disease with a very frequent common mutation among Caucasian populations – R49X (present in about 60% of the mutated alleles) – and several rare mutations, without a clear genotype/phenotype correlation.
The authors will present molecular data from the characterisation of 53 Portuguese patients, from 42 families, with McArdle disease. Our results reveal the presence of the R49X mutation in 60 of the alleles (57%), in accordance to what has been described to other Caucasian populations, being identified a total of 15 different mutations were identified.
These results allowed in many cases the diagnosis without the need of a muscle biopsy, but also provide valuable information for genetic counselling and to increase the knowledge about the molecular pathology of this disorder
