36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy
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.
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 self-reporting questionnaires. All tests were performed at baseline and every 12 months for 36 months of ERT.
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 non-significant changed.
Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT.
KeywordsForced Vital Capacity Enzyme Replacement Therapy Creatine Kinase Level Pompe Disease Pompe Patient
We thank the patients and their families for their patience and long-term cooperation. We also thank the technical team at the involved treatment centers. Research conducted in MC Johannes-Gutenberg-University, Mainz, Germany was supported by the European Union, 7th Framework Programme ‘EUCLYD- A European Consortium for Lysosomal Storage Diseases’ [health F2/2008 grant agreement 201678 to EM].
M. Deschauer, C. Kornblum, E. Mengel, W. Müller-Felber, M. Spranger, B. Schoser, S. Vielhaber have received lecturer honoraria from Genzyme Corporation.
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