Newborn screening for Pompe disease: synthesis of the evidence and development of screening recommendations

Abstract

Background: Pompe disease is a lysosomal storage disorder that leads to the accumulation of glycogen and subsequently to muscle weakness, organ damage, and death. Pompe disease is detectable through newborn screening, and treatment has become available recently.

Objective: Our goal was to review systematically all available evidence regarding screening for infantile Pompe disease to help policy makers determine whether Pompe disease should be added to their state's newborn screening battery.

Methods: We searched online databases, including Medline, clinicaltrials.gov, and the Computer Retrieval of Information on Scientific Projects database, as well as Web sites maintained by federal organizations (eg, the Food and Drug Administration) and other nonprofit or private organizations (eg, the March of Dimes and Genzyme Corp), by using the terms "glycogen storage disease type II," "Pompe disease," and "Pompe's disease." We also obtained preliminary findings from a screening program in Taiwan. Data were critically appraised and extracted by 2 investigators, one who is an expert in systematic review methods and the other who is an expert in Pompe disease.

Results: The prevalence of Pompe disease has been estimated to be approximately 1 case per 40,000. Small studies suggest that enzyme therapy is highly efficacious in infantile Pompe disease and that earlier intervention leads to improved outcomes. Screening cannot distinguish between infantile and late-onset Pompe disease. The current screening program in Taiwan has a high false-positive rate; however, the threshold was purposely set low to ensure that no case would be missed.

Conclusions: Pilot studies of screening are needed to identify the most efficacious strategy for screening and determine how to manage cases of late-onset Pompe disease before screening for Pompe disease is adopted widely by newborn screening programs.