NYMC Faculty Publications
Early Initiation of Enzyme Replacement Therapy as Facilitated by Newborn Screening Improves Health Outcomes Among Patients With Infantile-Onset Pompe Disease
Author Type(s)
Faculty
DOI
10.1016/j.gimo.2025.103478
Journal Title
Genetics in Medicine Open
First Page
103478
Document Type
Article
Publication Date
1-1-2026
Department
Pediatrics
Keywords
Enzyme replacement therapy, Immune tolerance induction, Newborn screening, Pompe disease
Disciplines
Medicine and Health Sciences
Abstract
PURPOSE: To assess the benefits of early enzyme replacement therapy (ERT) in patients with infantile-onset Pompe disease (IOPD). METHODS: A retrospective chart review of 17 IOPD (7 cross-reactive immunologic material [CRIM]-negative and 10 CRIM positive) who initiated ERT (alglucosidase alfa) ≤4 weeks of age and had ≥18 months follow-up was performed. RESULTS: Patients received starting doses of 20 mg/kg/every other week (n = 11), 20 mg/kg/week (n = 3), or 40 mg/kg/week (n = 3). Six CRIM-negative and 2 patients who were CRIM positive received immune tolerance induction (ITI) with Rituximab+Methotrexate+intravenous immunoglobulin. Five patients who were CRIM positive received transient low-dose methotrexate. All CRIM-negative patients were immune tolerant. Three patients who were CRIM positive developed high-sustained antibody titers (HSAT); 2 were immune tolerant after bortezomib-based ITI. One patient who was CRIM positive developed HSAT, was invasively ventilated, and succumbed at age 5.2 years. At the most recent follow-up (MRFU; 3.1-18.4 years), 16 patients were alive, ambulatory, feeding orally, invasive ventilator-free, and receiving high-dose ERT (median lifelong dose 2.76X; 1.36-4.00). All patients experienced left ventricular mass index and Glc reductions and for a subset, biomarkers were within normal limits at MRFU (left ventricular mass index:16/17, AST:9/17, CK:5/17, and Glc:5/16). CONCLUSION: These data highlight the benefits of early ERT initiation and ITI, along with high-dose ERT. Despite early treatment, patients with IOPD remain at risk of developing HSAT.
Recommended Citation
Desai, A. K., Rodriguez-Rassi, E., Parikh, S., Russo, R. S., Kronn, D., Hamm, J. A., Chang, I. J., Ortiz, D., McPheron, M., Lydigsen, H., DeArmey, S., Young, S. P., & Kishnani, P. S. (2026). Early Initiation of Enzyme Replacement Therapy as Facilitated by Newborn Screening Improves Health Outcomes Among Patients With Infantile-Onset Pompe Disease. Genetics in Medicine Open, 4, 103478. https://doi.org/10.1016/j.gimo.2025.103478
