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Lessons from late-onset Pompe disease identified by Newborn screening: A systematic review.
Myriam Boueri1, Jessica Doxey1, Tracy Boggs2
1Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States.
Molecular Genetics and Metabolism
|February 20, 2026
Summary
Newborn screening (NBS) for late-onset Pompe disease (LOPD) reveals earlier phenotypes and diverse clinical presentations. Early enzyme replacement therapy (ERT) may benefit select infants identified through NBS, highlighting the need for long-term follow-up and clear treatment guidelines.
Area of Science:
- Genetics and rare diseases
- Lysosomal storage disorders
- Newborn screening advancements
Background:
- Late-onset Pompe disease (LOPD) is a progressive neuromuscular lysosomal disorder.
- Newborn screening (NBS) enables earlier detection of LOPD, revealing a broader spectrum of disease than previously understood.
- Distinguishing LOPD from infantile-onset Pompe disease (IOPD) relies on the absence of early cardiomyopathy.
Purpose of the Study:
- To systematically review newborn screening (NBS) data for late-onset Pompe disease (LOPD) from Taiwan and the United States.
- To analyze clinical manifestations, genotypes, biomarkers, treatments, and follow-up data in LOPD cases identified through NBS.
- To understand the impact of NBS on LOPD diagnosis and management.
Main Methods:
- Systematic literature search of PubMed up to January 2026 using keywords: "Pompe disease," "late-onset Pompe disease," and "newborn screening."
- Inclusion of studies reporting LOPD diagnosed via NBS; exclusion of non-English articles and studies solely on infantile-onset Pompe disease.
- Data extraction included genotype, biomarkers, muscle imaging, enzyme replacement therapy (ERT) status, and outcomes; narrative synthesis due to data heterogeneity.
Main Results:
- The common splice site variant c.-32-13 T > G (IVS1) in GAA was absent in Taiwan but frequent in US cohorts, generally linked to milder LOPD phenotypes.
- Compound heterozygous individuals for IVS1 and another pathogenic GAA variant showed variable presentations, with some experiencing elevated biomarkers and early motor signs.
- Population-level data from Taiwan showed 21% of 39 LOPD cases initiated ERT between 1.6 months and 3 years; US data indicated early ERT initiation improved biochemical and motor outcomes in some NBS-identified infants.
Conclusions:
- Newborn screening (NBS) has expanded the understanding of previously unrecognized LOPD phenotypes.
- Heterogeneous follow-up protocols, lack of unified diagnostic criteria, and limited long-term data present challenges in LOPD management.
- Future research should focus on long-term follow-up, detailed phenotyping, and establishing clearer guidelines for ERT initiation in NBS-detected LOPD cases.
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