title: Electrocardiographic response to enzyme replacement therapy for Pompe disease.
abstract: OBJECTIVE
  Electrocardiogram (ECG) abnormalities are universal in infantile Pompe disease or glycogen storage disease type II, a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). Hallmarks of this disease include a shortened PR interval, an increased QT dispersion (QTd), and large left ventricular (LV) voltages. We evaluated the effect of recombinant human GAA (rhGAA) enzyme replacement therapy (ERT) on these ECG parameters in patients with infantile-onset Pompe disease.
  
  
  METHODS
  A total of 134 ECGs were evaluated from 19 patients (5 females and 14 males) with a median age of 5.5 months at the time of enrollment in open-label clinical trials exploring the safety and efficacy of ERT at a single center from 1999 to 2004. rhGAA was purified from genetically engineered Chinese hamster ovary cells overproducing GAA and infused intravenously at doses ranging from 10 mg/kg per week to 20 to 40 mg/kg every 2 weeks in patients with infantile-onset Pompe disease. The PR interval, QTd (longest to shortest QT), and LV voltage (SV1 + RV6) were blindly determined by two independent observers.
  
  
  RESULTS
  The median follow-up period was 6 months (range 2-30 months). The PR interval lengthened from 83 (42-110) ms to 107 (95-130) ms (P < .001), and the QTd decreased from 83 (40-125) ms to 53 (20-80) ms (P = .003). There were significant decreases in LV voltage (67 [17-83] mV vs. 48 [18-77] mV, P = .03), which correlated with decrease in LV mass on two-dimensional echocardiogram. There was no evident change in the QTc interval (429 [390-480] ms vs. 413 [370-450] ms, P = not significant).
  
  
  CONCLUSIONS
  rhGAA ERT for infantile Pompe disease results in an increase in PR interval and a decrease in both the QTd and the LV voltage. These results suggest that these ECG parameters may be useful markers of the severity of cardiac disease and the response to ERT treatment in patients with infantile Pompe disease.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Annette K
authors.initials: AK
authors.lastname: Ansong
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Li
authors.forename: Eva
authors.initials: E
authors.lastname: Nozik-Grayck
authors.forename: Richard
authors.initials: R
authors.lastname: Ing
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kravitz
authors.forename: Salim F
authors.initials: SF
authors.lastname: Idriss
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Kanter
authors.forename: Henry
authors.initials: H
authors.lastname: Rice
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D000520:alpha-Glucosidases / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; C509951:GAA protein, human; D000520:alpha-Glucosidases