Reversal of Cardiac Dysfunction after Enzyme Replacement in Patients with Infantile-Onset Pompe Disease Lei-Ru Chen, MD, Chun-An Chen, MD, Shuenn-Nan Chiu, MD, Yin-Hsiu Chien, MD, Ni-Chung Lee, MD, Ming-Tai Lin, MD, Wuh-Liang Hwu, MD, PhD, Jou-Kou Wang, MD, PhD, and Mei-Hwan Wu, MD, PhD Objective To compare the effects of enzyme replacement therapy (ERT) on cardiac performance in symptomatic and symptom-free infants with Pompe disease. Study design Patients diagnosed between 1983 and 2008 were identified. Before the initiation of ERT, systolic dysfunction appeared only in patients $5 months; thus we used this cut-point in age to divide clinically symptom- atic patients into early and late treatment groups (Clin-E and Clin-L). Newborn screening (NBS) identified symptom- free patients. Results Among a total of 40 patients, 14 received ERT: 5 in the Clin-L, 4 in the Clin-E, and 5 in the NBS groups. All patients showed cardiomegaly, hypertrophic myocardium, and elevated B-type natriuretic peptide (measured in the Clin-E and NBS groups). ERT improved the survival and outcomes. Regressed myocardial hypertrophy and lowered B-type natriuretic peptide level occurred after 1 to 6 months of ERT. Nonetheless, there were 2 deaths and 2 survivors requiring ventilator support in the Clin-L group. Despite the regressed QRS voltage and shortened QT dispersion, life-threatening arrhythmias were still observed in 3, but none in the NBS group. Conclusion ERT may restore the cardiac function in both symptomatic and symptom-free patients, but the beneficial effect may be unpredictable if given after the age of 5 months. (J Pediatr 2009;155:271-5). P ompe disease is an autosomal recessive disease caused by the deficiency of the glycolytic lysosomal enzyme acid a-glucosi- dase (GAA). This enzyme defect results in the accumulation of glycogen within the lysosomes, especially in smooth, skeletal, and cardiac muscle cells. 1 Patients with infantile-onset Pompe disease usually present with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy in early infancy. 2 A short PR interval and a large QRS complex are the characteristic electrocardiographic changes. 3 Most patients die of cardiopulmonary failure before the age of 1 year. 4-6 Enzyme replacement ther- apy (ERT) with recombinant human GAA has been recently shown to effectively reduce left ventricular (LV) mass, improve cardiac function and remodel the conduction abnormalities. 7-9 Furthermore, the success of newborn screening (NBS) for Pompe disease made early administration of ERT possible in symptom-free patients. 10 However, the impact of the timing of ERT initiation on the reversal of cardiac dysfunction has never been examined. The purpose of this study was to explore the association between clinical status at ERT initiation and the effects of ERT on cardiac performance in patients with infantile-onset Pompe disease. Methods Patients diagnosed with infantile-onset Pompe disease from January 1983 to March 2008 were identified from the patient da- tabase of the National Taiwan University Hospital. The diagnosis was confirmed by endogenous GAA enzyme activity being less than 5% of the normal mean in mononuclear blood cells. 10 Twenty-six patients were born before June 2002 (the pre-ERT era), and all died before ERT was available. An additional 14 patients were born after or survived to December 2002 (the post-ERT era) when ERT with intravenous recombinant human GAA (20mg/kg, every other week) was started in all patients. Data from the patients who did not receive ERT (n = 26) and the pre-ERT data from patients who later received ERT (n = 14) were used to investigate the natural course of ventricular dysfunction in infantile-onset Pompe disease. We found that systolic From the Department of Pediatrics (L.C., C.C., S.C., Y.C., M.L., W.H., J.W., M.W.) and Medical Genetics (N.L., W.H.), National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan Lei-Ru Chen and Chun-An Chen contributed equally to this paper. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright Ó 2009 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2009.03.015 BNP B-type natriuretic peptide ECG Electrocardiogram ERT Enzyme replacement therapy GAA Acid-a glucosidase LV Left ventricular LVEF Left ventricular ejection fraction LVMI Left ventricular mass index NBS Newborn screening QTc Corrected QT interval QTd QT dispersion 271