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Electrocardiographic response to enzyme replacement therapy for Pompe disease.
Genet Med 2006; 8(5):297-301GM

Abstract

PURPOSE

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).

CONCLUSION

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+Show Affiliations

Division of Pediatric Cardiology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16702879

Citation

Ansong, Annette K., et al. "Electrocardiographic Response to Enzyme Replacement Therapy for Pompe Disease." Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 8, no. 5, 2006, pp. 297-301.
Ansong AK, Li JS, Nozik-Grayck E, et al. Electrocardiographic response to enzyme replacement therapy for Pompe disease. Genet Med. 2006;8(5):297-301.
Ansong, A. K., Li, J. S., Nozik-Grayck, E., Ing, R., Kravitz, R. M., Idriss, S. F., ... Kishnani, P. S. (2006). Electrocardiographic response to enzyme replacement therapy for Pompe disease. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 8(5), pp. 297-301.
Ansong AK, et al. Electrocardiographic Response to Enzyme Replacement Therapy for Pompe Disease. Genet Med. 2006;8(5):297-301. PubMed PMID: 16702879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrocardiographic response to enzyme replacement therapy for Pompe disease. AU - Ansong,Annette K, AU - Li,Jennifer S, AU - Nozik-Grayck,Eva, AU - Ing,Richard, AU - Kravitz,Richard M, AU - Idriss,Salim F, AU - Kanter,Ronald J, AU - Rice,Henry, AU - Chen,Y T, AU - Kishnani,Priya S, PY - 2006/5/17/pubmed PY - 2006/7/11/medline PY - 2006/5/17/entrez SP - 297 EP - 301 JF - Genetics in medicine : official journal of the American College of Medical Genetics JO - Genet. Med. VL - 8 IS - 5 N2 - PURPOSE: 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). CONCLUSION: 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. SN - 1098-3600 UR - https://www.unboundmedicine.com/medline/citation/16702879/Electrocardiographic_response_to_enzyme_replacement_therapy_for_Pompe_disease_ L2 - http://dx.doi.org/10.1097/01.gim.0000195896.04069.5f DB - PRIME DP - Unbound Medicine ER -