Key Clinical Summary: Advancing Pompe Care – Expert Q&A: Real-World Challenges in LOPD Care

This is a micro-learning module summary of a presentation by Prof. Pascal Laforêt and Prof. John Vissing which you can find here. Before participating, please read our CME and disclosure information which can be found here.

This activity is supported by an independent medical educational grant from Amicus Therapeutics. This online education program has been designed for healthcare professionals globally (excluding the USA).

The Q&A section of this program is designed as a dynamic, expert-led forum to bridge the gap between clinical evidence and real-world application in Late-Onset Pompe Disease (LOPD). This interactive component allows healthcare professionals to engage directly with international experts to resolve uncertainties surrounding the heterogeneous phenotypes, subclinical monitoring, and complex therapy transitions defined in the European Triple-S framework.

Question: Should we be moving away from muscle biopsy as a primary diagnostic tool for LOPD in favor of genetic or dried blood spot (DBS) testing?

Summary of Answer: Muscle biopsy is no longer the preferred primary diagnostic tool because it frequently yields false negatives when vacuolar myopathy is absent. Experts now recommend initial screening via DBS testing or targeted genetic testing, with exome or whole-genome sequencing reserved for complex differential diagnoses.

Question: In patients with normal creatine kinase (CK) levels, what red flags should still prompt a suspicion of LOPD?

Summary of Answer: While ~90% of patients show mildly elevated CK, normal levels do not exclude LOPD. Clinicians should maintain a high index of suspicion when encountering "red flags" such as proximal and axial muscle weakness, tongue involvement, or unexplained respiratory insufficiency.

Question: Beyond skeletal muscle and respiratory systems, what other systemic manifestations should a multidisciplinary team monitor?

Summary of Answer: LOPD is a multi-systemic disorder; monitoring must extend to gastrointestinal symptoms, bladder dysfunction, and potential cerebrovascular risks, such as aneurysms, to ensure holistic patient management.

Question: Why is assessing Forced Vital Capacity (FVC) in the supine position more sensitive than standard sitting assessment?

Summary of Answer: Assessing both sitting and supine FVC is critical for detecting diaphragmatic involvement; as a drop of >20% when supine is a key indicator of respiratory decline. Professionals should also integrate Maximal Inspiratory/Expiratory Pressure (MIP/MEP) for a more comprehensive assessment.

Question: How should the "20% fat fraction rule" be applied when using muscle MRI to monitor stable patients?

Summary of Answer: Quantitative MRI can uncover subclinical progression even when functional scores remain stable. A fat fraction exceeding 20% in more than two muscles ften signals a transition into a more rapid progressive phase, providing a vital objective marker for therapy optimization.

Question: How do digital function metrics and smartphone apps improve upon traditional tests like the six-minute walk test?

Summary of Answer: Unlike periodic hospital-based tests, digital tools and wearables may offer continuous data that capture daily functional variability and subtle endurance loss, providing a more "linear" and accurate vision of disease progression.

Question: How is "non-response" to Enzyme Replacement Therapy (ERT) defined in the long term, especially when many patients decline after 3–5 years?

Summary of Answer: Long-term "non-response" is complex, as secondary decline may reflect the natural history of the disease. Application of the European Triple-S framework—which uses objective switch criteria based on clinical milestones and imaging biomarkers—is essential for making shared decisions on transitioning or optimizing therapy.

Content was accurate at the time of publication.