Meta-opinion: from screening to diagnosis of Pompe disease – a European perspective

ABSTRACT

Introduction: After 10 years of alglucosidase alfa therapy of Pompe disease, elements of the disease remain unsolved e.g. how and whom to screen, or when to start and stop therapy.

Areas covered: In this paper, we review published studies for screening strategies by dried blood spot testing (DBS) in Pompe disease of all ages.

Expert opinion: To find patients with late-onset Pompe disease early, a targeted screening strategy was demonstrated to be highly successful. Since the introduction of alglucosidase alfa as an effective treatment for Pompe disease at all ages, there has not yet been another licensed pharmacologic intervention. Up to a third of Pompe patients need alternative therapies. New therapies will need to show a significantly greater sustained benefit for Pompe patients with a better balance of cost effectiveness. Finally, as another consequence, DBS, with the high incidence of positive samples from patients with late-onset Pompe disease, cannot be recommended currently to be included in newborn screening. Presently, screening of infants seems feasible with a two-tier strategy combining DBS with cardiac and pulmonary diagnostics. This approach avoids reporting late-onset Pompe disease (LOPD), which shows unpredictable phenotypes and the therapeutical outcome remains uncertain.

KEYWORDS:

• Clinical trials
• DBS
• glycogen storage disease type 2
• Pompe disease
• screening

Article highlights

• Current status of GAA DBS in Pompe disease at all ages

• Cumulative positive sensitivity for early detection in targeted populations

• Clear advice on the use of GAA DBS

• Recommendation not to use GAA DBS in newborn screening

This box summarizes key points contained in the article.

Acknowledgments

The authors thank all patients and the patient support groups for the ongoing help and cooperation.

Declaration of interest

Z Lukacs and B Schoser have received research support, honoraria, and travel funding from Sanofi-Genzyme and BioMarin Ltd. during the past 5 years. B Schoser received honoraria and travel funding from Amicus Therapeutics, and Audentes Therapeutics. B Schoser is member of the Sanofi-Genzyme Pompe Disease Global Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.