LOPD care: From screening to treatment

By Laura Boyd

Diagnostic delays in LOPD can exceed 10 years, with 75% of patients often misdiagnosed

Late-onset Pompe disease (LOPD) is a progressive, multisystem disorder that can often remain undetected until irreversible muscle damage occurs. Despite advances in enzyme replacement therapy (ERT), diagnostic delays and suboptimal monitoring persist, compounded by complexities introduced by newborn screening and variants of unknown significance (VUS). Emerging tools – such as biomarkers and advanced imaging – offer opportunities for earlier intervention, yet standardized protocols are lacking. Clinicians face nuanced decisions around treatment initiation, therapy switching, and multidisciplinary coordination in the absence of head-to-head trial data. Addressing these gaps is critical to optimize outcomes and reduce disease burden in patients with LOPD.

What are the key challenges in diagnosing LOPD early and accurately?

Due to nonspecific symptoms and disease rarity, diagnostic delays and misdiagnosis remain common, with patients consulting multiple specialists before confirmation.

Newborn screening improves early detection but introduces complexities in referral pathways, as detection of VUS can delay intervention and complicate care planning.

How does newborn screening impact management strategies for asymptomatic patients?

Newborn screening identifies presymptomatic individuals. While early detection offers potential benefits, standardized protocols for long-term follow-up are lacking.

Clinicians must balance proactive monitoring with psychological considerations for patients and families during extended asymptomatic periods.

Which biomarkers are most useful for monitoring LOPD progression and treatment response?

Biomarkers can provide insights into muscle damage and treatment response, including:

• Urinary hexose tetrasaccharide (Hex4)
• Serum creatine kinase (CK)

However, interpretation requires expertise, and levels may be normal in presymptomatic patients. Combining biomarker data with imaging and functional assessments can improve detection of subclinical progression.

What factors influence therapy selection and switching in LOPD?

Treatment decisions are complicated by:

• Heterogeneous disease progression 
• Patient preferences
• Limited head-to-head trial data

Real-world evidence, magnetic resonance imaging (MRI) findings, and shared decision-making frameworks must be considered when transitioning between therapies to optimize outcomes.

How do next-generation enzyme replacement therapies compare in efficacy and safety?

Avalglucosidase alfa and cipaglucosidase alfa with miglustat offer improved glycogen targeting and cellular uptake compared with alglucosidase alfa.

• COMET trial data favor avalglucosidase alfa over standard therapy
• PROPEL trial data suggest benefits from switching to cipaglucosidase alfa plus miglustat

Comparative evidence remains limited, emphasizing individualized care.

Key takeaways

• Diagnostic delays and VUS interpretation remain major barriers to early, accurate LOPD diagnosis
• Newborn screening improves detection but creates uncertainty in monitoring and treatment initiation for asymptomatic patients
• Biomarkers are valuable but require integration with imaging for effective monitoring
• Therapy selection and switching depend on individualized factors and limited comparative data
• Next-generation ERTs show promise, but real-world evidence and head-to-head trials are lacking

Developed by EPG Health for Medthority, independently of any sponsor.