P.214 - Interim analysis of an investigator-initiated multi-site late-onset Pompe disease screening study

Abstract

Late-onset Pompe disease (LOPD) is an inherited lysosomal storage disease, in which the enzyme acid alpha-glucosidase (GAA) is deficient. It is characterized by proximal limb-girdle muscle weakness and respiratory insufficiency. The disease is progressive, and if left untreated, may result in significant motor disability and respiratory failure. As of 2010, nine studies have been published documenting the incidence of LOPD. In the U.S. the incidence of the disease is 1 in 40,000. Recently Pompe disease has become part of the newborn screening panel in multiple states. Due to the relatively high frequency of Pompe disease reported, we would expect that large medical centers specializing in neuromuscular diseases would see a higher incidence of LOPD among their patients than what is currently reported. The objective of this multi-site investigator-initiated study is to determine true prevalence of LOPD in patients presenting to academic tertiary geographically disparate neuromuscular centers in the US and Canada using specific selection criteria. Clinic patients who present with symptoms of undiagnosed proximal muscle weakness, neck weakness or elevation of creatinine kinase, are screened for LOPD. Total recruitment goal is 1,500 subjects across 14 sites. Since study initiation we have enrolled 465 subjects. 42/465 (9.0%) had abnormal GAA enzyme levels (<10 pmol/punch/hr). 5/465 (1.1%) were diagnosed, confirmed by gene sequencing, with LOPD. 6/465 (1.3%) were carriers of one GAA gene mutation, 3/465 (0.6%) had one GAA variant of uncertain significance, and 3/465 (0.6%) had the pseudodeficiency allele. The study is ongoing however behind schedule. The feasibility of enrolling 1500 subjects in an investigator-initiated study has proven to be more challenging than anticipated.