Phenotype modulators in myophosphorylase deficiency

Andrea Martinuzzi, Elena Sartori, Marina Fanin, Annachiara Nascimbeni, Lucia Valente, Corrado Angelini, Gabriele Siciliano, Tiziana Mongini, Paola Tonin, Giuliano Tomelleri, Antonio Toscano, Luciano Merlini, Laurence A. Bindoff, Stefano Bertelli

Research output: Contribution to journalArticlepeer-review


Myophosphorylase deficiency is characterized by exercise intolerance, muscle cramps, and recurrent myoglobinuria. Some patients are severely affected, whereas others are minimally affected or asymptomatic. The molecular basis of the disease has been elucidated but does not provide an explanation for the clinical variability. In a large cohort of patients with myophosphorylase deficiency, we tested the hypothesis that polymorphic variants in either myoadenylate deaminase (MADA) or angiotensin-converting enzyme (ACE) could act as modulators of phenotype expression. Forty-seven patients were evaluated. Clinical severity was assessed according to a severity scale of four grades. MADA activity was studied by histochemical and biochemical analysis of muscle, and the Q12X mutation in the adenine monophosphate deaminase 1 gene (AMPDI) and the insertion/deletion polymorphism in the ACE gene were assessed genetically. A complete MADA defect together with the Q12X mutation was detected in one severely affected patient. Eleven patients were heterozygous for the Q12X mutation. There was no association between clinical grading and MADA status. In contrast, we found a highly significant (p <0.01) association between ACE genotype and clinical severity, with strong correlation between severe phenotype and number of D alleles. We show that ACE insertion/deletion polymorphism may play a significant role as phenotype modulator in McArdle's disease.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalAnnals of Neurology
Issue number4
Publication statusPublished - Apr 1 2003

ASJC Scopus subject areas

  • Neuroscience(all)


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