36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy

Objectives Glycogen storage disease type 2(GSD2)/Pompe disease is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Methods We present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 38 adult-onset GSD2 patients (20 female, 18 male) with a mean age at disease onset of 36.2±10.5 years. Mean delay between symptom onset and start of ERT was 14.5±7.2 years. Assessments included serial Walton Gardner Medwin scale, arm function tests, timed 10-meter walk tests, 4-stair climb tests, modified Gowers' maneuvers, 6-minute walk test (6MWT), MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels, and SF-36 selfreporting questionnaires. All tests were performed at baseline and every 12 months for 36 months of ERT. Results In the 6MWT we found 21 patients able to walk at baseline a mean distance of 312±165.5 m, improving to 344±165.8 m after 12 months (p=0.006), remaining at 356.4±155.9 m at 24 months (p=0.033), and declining to 325.6±174.8 m after 36 months of ERT (p=0.49, n.s.). The mean FVC in 28 patients was 80.27±14.08% of predicted normal at baseline, after 12 months 79.19±13.09%, at 24 months 78.62±16.55%, and 77.19±18.05% after 36 months. Only mean CK levels were significantly decreased by 8.8% (p=0.041). All other tests were statistically nonsignificant changed. Conclusion Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT.