| Title: |
Early initiation of enzyme replacement therapy as facilitated by newborn screening improves health outcomes among patients with infantile-onset Pompe disease |
| Authors: |
Desai, Ankit K.; Rodriguez-Rassi, Eleanor; Parikh, Suhag; Sanchez Russo, Rossana; Kronn, David; Hamm, J. Austin; Chang, Irene J.; Ortiz, Damara; McPheron, Molly; Lydigsen, Holly; DeArmey, Stephanie; Young, Sarah P.; Kishnani, Priya S. |
| Contributors: |
Medical and Molecular Genetics, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Enzyme replacement therapy; Immune tolerance induction; Newborn screening; Pompe disease |
| Description: |
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 Glc4 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 Glc4:5/16). 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Genetics in Medicine Open; https://hdl.handle.net/1805/53977 |
| Availability: |
https://hdl.handle.net/1805/53977 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.8E15F6FC |
| Database: |
BASE |