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


CONCLUSIONS
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.
Levine
Jami C
JC
Department of Cardiology, Children's Hospital Boston and Pediatrics, Harvard Medical School, Boston, MA 02115, USA. jami.levine@cardio.chboston.org
Kishnani
Priya S
PS
Chen
Y T
YT
Herlong
J Rene
JR
Li
Jennifer S
JS
D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D013902:Radiography, Thoracic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D000520:alpha-Glucosidases