Clinical and laboratory features of patients with myophosphorylase deficiency (McArdle disease).

Mutations of PYGM, the gene encoding human myophosphorylase, produce a metabolic myopathy characterised by exercise intolerance and, in some patients, myoglobinuria. To illustrate the clinical and laboratory features of myophosphorylase deficiency, we describe 10 patients diagnosed in Auckland, New Zealand, between 1989 and 2009. We review the clinical, biochemical, and histologic features and the results of mutation analysis. All patients reported exercise intolerance since childhood or the teenage years, starting within minutes of moderate or intense exertion. The "second wind" phenomenon, or myoglobinuria, were each reported in about half the patients. The serum creatine kinase concentration was elevated in all patients where this had been measured. Muscle biopsies revealed subsarcolemmal vacuolation and histochemical absence of myophosphorylase. Analysis of PYGM showed mutations in all alleles, most commonly Arg49Ter or Gly204Ser. One patient harbored a novel mutation, Pro488Arg, predicted to seriously disrupt the tertiary structure of the enzyme. Myophosphorylase deficiency produces a fairly uniform set of symptoms, and consistent elevation of the serum creatine kinase concentration. The diagnosis can be confirmed in most patients by mutation analysis using a blood sample.