Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes Chia-Feng Yang, MD 1,2 , Chen Chang Yang, PhD 2,3 , Hsuan-Chieh Liao, MSc 4,5 , Ling-Yi Huang, RN 6 , Chuan-Chi Chiang, PhD 4 , Hui-Chen Ho, BS 7 , Chih-Jou Lai, MD 8 , Tzu-Hung Chu, MD 1 , Tsui-Feng Yang, MD 8 , Ting-Rong Hsu, MD 1 , Wen-Jue Soong, PhD 1 , and Dau-Ming Niu, MD 1,9 Objective To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. Methods In this nationwide program, 669 797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. Results After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid a-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6  1.3 months, the same age as normal children. Conclusions ERT for patients with IOPD should be initiated as early as possible before irreversible damage oc- curs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes. (J Pediatr 2016;169:174-80). P ompe disease is an autosomal-recessive lysosomal storage disorder characterized by the deficiency of acid a-glucosidase (GAA), 1,2 which leads to the progressive accumulation of glycogen in numerous types of cells and tissues. 3,4 A broad spectrum of clinical phenotypes is observed, ranging from the severe, rapidly progressive infantile-onset Pompe disease (IOPD) characterized by cardiac involvement to the attenuated, late-onset Pompe disease. 5-7 Early enzyme-replacement ther- apy (ERT) with recombinant human alglucosidase alpha (Myozyme; Genzyme, Boston, Massachusetts) can prolong survival and improve the long-term outcome of patients with IOPD. 6,8,9 Nevertheless, it remains unknown whether therapeutic out- comes differ between very early (10 days of age) and early (1 month of age) IOPD treatment. Newborn screening is the only way to initiate the early diagnosis and treatment of Pompe disease. 8,9 However, even when the newborn screening is used, the earliest mean age at the start of ERT is about 21 days. 10 The Taipei Veterans General Hospital (TVGH) began Pompe newborn screening in 2008, testing approximately two-thirds of the newborn population in Taiwan. 4,6,8 By 2010, we had established an effective newborn screening program with rapid diagnostic strategies, 4 and almost all of the infants with suspected IOPD could be diagnosed correctly within 2 hours and receive ERT within 4 hours of admission. With such an effective system, most of our patients with IOPD started their ERT at about 11 days of age. In this 6-year cohort study, we report the prognosis of 14 patients with IOPD who received very early ERT and compare these results with those of similar cohorts. Furthermore, we compare the outcomes of 5 patients with IOPD who have identical GAA gene mutations to disclose possible differences between few days earlier treatment. Methods Pompe disease screening was added to the newborn screening system in Taiwan in 2008. In this nationwide program, 669 797 newborns were screened for Pompe From the 1 Department of Pediatrics, Taipei Veterans General Hospital; 2 Institute of Environmental and Occupational Health Sciences, National Yang-Ming University; 3 Division of Clinical Toxicology & Occupational Medicine, Taipei Veterans General Hospital; 4 The Chinese Foundation of Health Neonatal Screening Center; 5 Institute of Clinical Medicine, National Yang-Ming University; 6 Division of Nephrology, Department of Internal Medicine, Taipei City Hospital- Heping Fuyou Branch; 7 Taipei Institute of Pathology; 8 Physical Medicine and Rehabilitation Department, Taipei Veterans General Hospital; and 9 Department of Pediatrics, School of Medicine, National Yang-Ming University, Taipei, Taiwan Supported by the Taipei Veterans General Hospital (104DHA0100423). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2016 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpeds.2015.10.078 AST Aspartate aminotransferase Bayley-III Bayley Scale of Infant and Toddler Development, Third Edition CK Creatine kinase CRIM Cross-reactive immunologic ERT Enzyme-replacement therapy GAA Acid a-glucosidase IOPD Infantile-onset Pompe disease LDH Lactate dehydrogenase LVMI Left ventricular mass index PDMS-II Peabody Development Motor Scale, Second Edition TVGH Taipei Veterans General Hospital 174