Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Levine, JC; Kishnani, PS; Chen, YT; Herlong, JR; Li, JS

Published Date

  • November 2008

Published In

Volume / Issue

  • 29 / 6

Start / End Page

  • 1033 - 1042

PubMed ID

  • 18661169

Pubmed Central ID

  • PMC2683920

International Standard Serial Number (ISSN)

  • 0172-0643

Digital Object Identifier (DOI)

  • 10.1007/s00246-008-9267-3


  • eng

Conference Location

  • United States