title: Molecular analysis and protein processing in late-onset Pompe disease patients with low levels of acid α-glucosidase activity.
abstract: BACKGROUND
  Pompe disease (glycogen storage disease type II, acid maltase deficiency) is caused by deficiency of lysosomal acid α-glucosidase (GAA). A few late-onset patients have been reported with skin fibroblast GAA activity levels of <2%.
  
  
  METHODS
  We measured GAA activity in skin fibroblasts from 101 patients with late-onset Pompe disease. Whenever possible, we performed Western blot analysis and correlated the results with GAA activity and GAA gene mutations.
  
  
  RESULTS
  Thirteen patients (13%) had skin fibroblast GAA activity of <1% of normal. Although there was wide genetic heterogeneity, none of these patients carried the common late-onset mutation c.-32-13T > G. We performed Western blot on 11 patients with <1% GAA activity. All produced GAA protein that was at lower levels and/or was abnormally processed.
  
  
  CONCLUSIONS
  There is no common mutation associated with <1% GAA activity in late-onset Pompe disease patients. Most patients produce unprocessed forms of GAA protein compared with patients with higher GAA activity.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA. bali0001@mc.duke.edu
authors.forename: Deeksha S
authors.initials: DS
authors.lastname: Bali
authors.forename: Adviye A
authors.initials: AA
authors.lastname: Tolun
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goldstein
authors.forename: Jian
authors.initials: J
authors.lastname: Dai
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D015153:Blotting, Western / Q000379:methods; D002648:Child; D004789:Enzyme Activation / Q000235:genetics; D006009:Glycogen Storage Disease Type II / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D046188:Protein Modification, Translational / Q000235:genetics*; D055815:Young Adult; D000520:alpha-Glucosidases / Q000235:genetics* / Q000378:metabolism*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases