Minimally symptomatic mcardle disease, expanding the genotype-phenotype spectrum

摘要

Introduction: We report the clinical, biochemical, and molecular findings in a Cypriot family with minimally symptomatic McArdle disease. Methods: Myophosphorylase in muscle was assessed by histochemistry, quantitative spectrophotometry, and western blot analysis. Mutation identification was performed by PCR amplification of all PYGM exons, followed by bidirectional sequencing. Screening for the new mutation was performed by restriction enzyme analysis. Results: We found that a novel c.1151C>T transition in exon 10 of the myophosphorylase gene (PYGM) is associated with minimally symptomatic McArdle disease. Homozygous carriers displayed an ischemic exercise response characterized by a blunted increase in post-exercise blood lactate levels in conjunction with an exaggerated increase in ammonia. Myophosphorylase activity in muscle was 3.75% of normal, whereas the size and abundance of the enzyme were unaffected. Conclusions: These findings expand the genotype-phenotype spectrum of McArdle disease and suggest that enzymatic activity as low as 4% may be sufficient to ameliorate the phenotype. Muscle Nerve52: 891-895, 2015