# Comprehensive review of recent advances in Pompe disease: pathogenesis, management, and future directions

## TL;DR

This paper reviews recent progress in understanding and treating Pompe disease, focusing on new therapies and monitoring technologies.

## Contribution

The paper provides a comprehensive synthesis of recent advances in Pompe disease management and future therapeutic strategies.

## Key findings

- Next-generation enzyme replacement therapies improve outcomes and safety in Pompe disease.
- Digital health technologies can detect motor impairment in presymptomatic stages.
- Emerging gene therapy and AAV vectors offer potential for better CNS targeting.

## Abstract

Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid alpha-glucosidase (GAA), leading to pathological glycogen accumulation in multiple tissues. This review synthesizes recent progress in understanding and managing Pompe disease, encompassing advances in newborn screening (NBS), novel biomarkers, next-generation enzyme replacement therapies (ERTs), gene therapy, and digital health technologies (DHTs) for monitoring. We also examine the associated economic burden and mortality patterns. Next-generation ERTs, including avalglucosidase alfa and cipaglucosidase alfa combined with miglustat, have improved outcomes and safety. Emerging strategies like transferrin receptor-mediated ERT and muscle-targeted adeno-associated virus (AAV) vectors show promise for overcoming current limitations, including central nervous system (CNS) involvement. DHTs enable sensitive detection of motor impairment even in presymptomatic stages. Despite progress, challenges remain in early detection, long-term management, and healthcare resource allocation. Future success requires integrated strategies combining NBS, innovative therapeutics, sensitive monitoring, and supportive policies.