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Early enzyme replacement therapy in late onset Pompe disease diagnosed by newborn screening
Abstract   Peer reviewed

Early enzyme replacement therapy in late onset Pompe disease diagnosed by newborn screening

Laura E. Case, Erin Huggins, Harrison N. Jones, Lisa D. Hobson-Webb, Deborah R. McMechan, Neelam A. Makhijani, Erica Nading, Steven A. Moore and Priya S. Kishnani
Molecular genetics and metabolism, Vol.147(2), 109357
02/2026
DOI: 10.1016/j.ymgme.2025.109357

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Abstract

Background and Objectives: Newborn screening (NBS) now allows for early detection and clinical monitoring in infants and children with late-onset Pompe disease (LOPD), potentially identifying those needing early enzyme replacement therapy (ERT). Early symptom onset has been reported in LOPD, but with a paucity of information on when to initiate ERT and on outcomes with early treatment. We report our experience at Duke University Medical Center with seven symptomatic children diagnosed with LOPD by NBS, harboring the common splice site variant c.-32-13 T > G, and a 2nd pathogenic or likely pathogenic variant, started early on ERT. Methods: All participants underwent periodic multidisciplinary evaluations including kinematic analysis of posture/movement; standardized assessments of gross motor, speech-language, and feeding/swallowing; serum and urine biomarker analysis; and quantitative muscle ultrasound. Results: Prior to initiation of ERT, all participants showed kinematic deficits and persistently elevated serum creatine kinase (CK). Median age at ERT initiation was 8.2 months (range: 2-20 months) with 6/7 showing standardized motor scores 10th percentile +/or declining. All started on alglucosidase alfa, later transitioning to avalglucosidase alfa without complications. At latest evaluation, all demonstrated motor improvement and normalization of CK. Conclusions: Data presented here supports existing evidence that infants and children with LOPD can present with early symptom onset and may benefit from early ERT. While further study is needed, we showcase the early features of LOPD, benefits from early ERT, and the importance of comprehensive multidisciplinary evaluation of LOPD diagnosed via NBS, allowing timely intervention for those that may benefit from early ERT. Funding/Support: This study was funded in part by a grant from Amicus Therapeutics, Inc. and in part by a grant from Sanofi Genzyme (Cambridge, Massachusetts, USA).

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