Myophosphorylase deficiency (McArdle disease): clinical and laboratory features in seven cases
Purpose: To demonstrate the typical clinical and laboratory features of myophosphorylase deficiency and review our experience with the molecular analysis of PYGM.
Methods: Hospital notes, laboratory results and muscle biopsies were reviewed. Patients were included if they had been seen by one of the authors (DH) and had myophosphorylase deficiency demonstrated by muscle histochemistry. Muscle biopsies were obtained under local anaesthesia and cryostat sections from flash-frozen muscle were examined histologically, which included myophosphorylase histochemistry. DNA was prepared from blood or frozen muscle by a guanidine thiocyanate method and 33 exons amplified by PCR.
Results: Symptoms were present since early childhood and consisted of muscle discomfort provoked by moderate exercise, usually forcing patients to interrupt their physical activity. The second wind phenomenon was reported by three patients. Three patients reported discomfort in jaw muscle with forceful chewing. One or more episodes of myoglobinuria had occurred in three patients. Limb weakness, usually mild, was found in three patients. The serum creatine kinase (CK) was elevated in all patient where this had been measured, always at least 2.5-fold higher than the upper limit of normal.
Six patients were heterozygous (4) or homozygous (2) for R49X, the common mutation in myophosphorylase deficiency. Three of the heterozygous patients harboured another common mutation, G204S. The fifth 5 harboured the R49X mutation and 2336_2338delA, a mutation previously reported in a consanguineous Turkish family. The remaining patient harboured two novel mutations.
Conclusion: The clinical presentation of patients with myophosphorylase deficiency is in our experience strikingly uniform. Analysis of the PYGM gene showed the common mutations in six patients and two novel mutations in the remaining patient.