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In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
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Infantile-onset Pompe disease entering adulthood: Insights from 2 decades of enzyme replacement therapy experience

Neha Regmi1, Daniel Kenney-Jung2, Grace Stafford1

  • 1Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC.

Genetics in Medicine : Official Journal of the American College of Medical Genetics
|September 27, 2025
PubMed

Insights

Long-term enzyme replacement therapy (ERT) in infantile-onset Pompe disease survivors preserves heart and lung function into adulthood. However, persistent multisystem issues indicate a need for earlier diagnosis and improved treatments.

Area of Science:

  • Neurology
  • Genetics
  • Pediatrics

Background:

  • Infantile-onset Pompe disease (IOPD) is a rare genetic disorder.
  • Enzyme replacement therapy (ERT) is a primary treatment for IOPD.
  • Long-term outcomes of ERT in adult survivors of IOPD are not well-documented.

Purpose of the Study:

  • To evaluate the long-term clinical outcomes of adult participants with CRIM-positive infantile-onset Pompe disease (IOPD) treated with ERT.
  • To assess multisystem involvement and biomarker trends in these patients.
  • To analyze central nervous system (CNS) involvement using the Modified Fazekas Score.

Main Methods:

  • Retrospective review of medical records for 11 participants with CRIM-positive IOPD initially reported in 2012.
  • Evaluation of central nervous system involvement via brain MRI and Modified Fazekas Score.
  • Tracking of cardiac, respiratory, and functional outcomes over time.

Main Results:

  • Eight of 11 participants survived to adulthood (median age 19.6 years).
  • ERT initiated in infancy (0.2-6 months) with dose escalation to alglucosidase alfa 40 mg/kg/week showed cardiac hypertrophy resolution and preserved respiratory function.
  • Persistent morbidities included flaccid dysarthria, ptosis, sensorineural hearing loss, and wheelchair dependence; CNS white matter hyperintensities remained mild to moderate.
  • Cognitive function remained stable in survivors.

Conclusions:

  • Long-term ERT is crucial for preserving cardiac and respiratory function in adult IOPD survivors.
  • Multisystem morbidity persists, underscoring the need for earlier diagnosis.
  • Novel therapies targeting muscle and CNS are required for comprehensive disease management.
Abstract

Keywords:
Cardiac functionEnzyme replacement therapyInfantile-onset Pompe diseaseLong-term survivorsMuscle weakness

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