title: Minimally symptomatic mcardle disease, expanding the genotype-phenotype spectrum.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Petros
authors.initials: P
authors.lastname: Petrou
authors.affiliation: Neurology Clinics A & C, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus.
authors.forename: Marios
authors.initials: M
authors.lastname: Pantzaris
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Maria
authors.initials: M
authors.lastname: Dionysiou
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Anthi
authors.initials: A
authors.lastname: Drousiotou
authors.affiliation: Neurology Clinics A & C, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kyriakides
mesh_terms: D000328:Adult; D005838:Genotype; D006012:Glycogen Storage Disease Type V / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype
keywords: McArdle disease; exercise test; lactate; mutation; myophosphorylase