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

• Published in: Journal of inherited metabolic disease 2012-09, Vol.35 (5), p.837-845
• Main Authors: Regnery, Caroline, Kornblum, Cornelia, Hanisch, Frank, Vielhaber, Stefan, Strigl-Pill, Nicola, Grunert, Birgit, Müller-Felber, Wolfgang, Glocker, Franz Xaver, Spranger, Matthias, Deschauer, Marcus, Mengel, Eugen, Schoser, Benedikt
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; alpha-Glucosidases - adverse effects; alpha-Glucosidases - therapeutic use; Biochemistry; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Creatine Kinase - metabolism; Enzyme Replacement Therapy - methods; Errors of metabolism; Female; Follow-Up Studies; Glycogen Storage Disease Type II - drug therapy; Glycogen Storage Disease Type II - enzymology; Glycogen Storage Disease Type II - metabolism; Human Genetics; Humans; Internal Medicine; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Original Article; Pediatrics; Respiratory Function Tests - methods; Treatment Outcome; Walking
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-012-9451-8

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 self-reporting 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 non-significant 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.