McArdle disease (gycogenosis type V): analysis of clinical, biological and genetic features of five French patients

INTRODUCTION: McArdle disease (glycogenosis type V) is an autosomal recessive metabolic myopathy. Defect in glycogen breakdown is due to mutations of the gene for myophosphorylase (PYGM). Among patients of the department, we searched for correlations between disease phenotype, biochemistry analysis of muscle samples and PYGM genotype. METHODS: We included five patients whose muscle biopsy showed deposits of glycogen and negative histochemical staining for myophosphorylase. RESULTS: All patients exhibited exercise intolerance and high serum CK levels (mean 4400). Two of them had an acute renal insufficiency caused by rhabdomyolysis. One patient developed moderate late-onset muscle weakness of the proximal part of upper limbs. Muscle glycogen concentration was high (three times the normal). Myophosphorylase activity was undetectable in four muscle samples out of five. Two patients were homozygous and two other heterozygous for the R50X mutation of PYGM. The other one had a novel missense mutation S814N. Patients homozygous for R50X mutation had higher CK levels (8080 versus 1457, p=0.046), but disease severity and muscle glycogen concentrations were equivalent. CONCLUSIONS: Our patients had typical clinical and laboratory features of McArdle disease. Diagnosis was suggested by exercise intolerance with high CK levels. The R50X mutation was the most common (60% of the mutated alleles). We found no relationship between clinical severity, PYGM genotype and biochemistry analysis of muscle samples.