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Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease.
Pediatr Cardiol 2008; 29(6):1033-42PC

Abstract

BACKGROUND

Infantile Pompe disease (glycogen storage disease type 2) is a fatal disorder caused by deficiency of acid alpha-glucosidase. This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle. The disease is characterized by profound hypotonia, poor growth, organomegaly, and cardiomegaly. Severe hypertrophic cardiomyopathy often is present in early infancy, and most patients die of cardiac or respiratory failure in the first year of life. This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy (ERT).

METHODS

Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA (rhGAA) for 1 year. Cardiac monitoring included echocardiography, electrocardiograms (ECGs), chest radiographs, and clinical cardiac evaluation at 4, 8, 12, 24, 36, and 52 weeks. At 52 weeks, 6 patients were alive.

RESULTS

Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT, with near normalization of posterior wall thickness, ventricular mass, and ventricular size. Systolic ventricular function was preserved despite rapid changes in ventricular mass and size. Concomitantly, ECGs documented lengthening of the PR interval and decreased ventricular voltages, whereas chest radiographs documented a decreased cardiothoracic ratio. Symptoms of pulmonary congestion were diminished, and survival was improved.

CONCLUSION

The cardiovascular system responds quickly and strikingly to ERT with rhGAA, suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells. Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival.

Authors+Show Affiliations

Department of Cardiology, Children's Hospital Boston and Pediatrics, Harvard Medical School, Boston, MA 02115, USA. jami.levine@cardio.chboston.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18661169

Citation

Levine, Jami C., et al. "Cardiac Remodeling After Enzyme Replacement Therapy With Acid Alpha-glucosidase for Infants With Pompe Disease." Pediatric Cardiology, vol. 29, no. 6, 2008, pp. 1033-42.
Levine JC, Kishnani PS, Chen YT, et al. Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatr Cardiol. 2008;29(6):1033-42.
Levine, J. C., Kishnani, P. S., Chen, Y. T., Herlong, J. R., & Li, J. S. (2008). Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatric Cardiology, 29(6), pp. 1033-42. doi:10.1007/s00246-008-9267-3.
Levine JC, et al. Cardiac Remodeling After Enzyme Replacement Therapy With Acid Alpha-glucosidase for Infants With Pompe Disease. Pediatr Cardiol. 2008;29(6):1033-42. PubMed PMID: 18661169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. AU - Levine,Jami C, AU - Kishnani,Priya S, AU - Chen,Y T, AU - Herlong,J Rene, AU - Li,Jennifer S, Y1 - 2008/07/26/ PY - 2007/05/10/received PY - 2008/06/24/accepted PY - 2008/03/25/revised PY - 2008/7/29/pubmed PY - 2009/2/12/medline PY - 2008/7/29/entrez SP - 1033 EP - 42 JF - Pediatric cardiology JO - Pediatr Cardiol VL - 29 IS - 6 N2 - BACKGROUND: Infantile Pompe disease (glycogen storage disease type 2) is a fatal disorder caused by deficiency of acid alpha-glucosidase. This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle. The disease is characterized by profound hypotonia, poor growth, organomegaly, and cardiomegaly. Severe hypertrophic cardiomyopathy often is present in early infancy, and most patients die of cardiac or respiratory failure in the first year of life. This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy (ERT). METHODS: Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA (rhGAA) for 1 year. Cardiac monitoring included echocardiography, electrocardiograms (ECGs), chest radiographs, and clinical cardiac evaluation at 4, 8, 12, 24, 36, and 52 weeks. At 52 weeks, 6 patients were alive. RESULTS: Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT, with near normalization of posterior wall thickness, ventricular mass, and ventricular size. Systolic ventricular function was preserved despite rapid changes in ventricular mass and size. Concomitantly, ECGs documented lengthening of the PR interval and decreased ventricular voltages, whereas chest radiographs documented a decreased cardiothoracic ratio. Symptoms of pulmonary congestion were diminished, and survival was improved. CONCLUSION: The cardiovascular system responds quickly and strikingly to ERT with rhGAA, suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells. Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival. SN - 0172-0643 UR - https://www.unboundmedicine.com/medline/citation/18661169/Cardiac_remodeling_after_enzyme_replacement_therapy_with_acid_alpha_glucosidase_for_infants_with_Pompe_disease_ L2 - https://dx.doi.org/10.1007/s00246-008-9267-3 DB - PRIME DP - Unbound Medicine ER -