Abstract
Objectives
Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.
Methods
Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO2), and muscle enzymes were assessed every 6 months.
Results
The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS > 3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO2 decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT.
Conclusions
Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.
Similar content being viewed by others
References
Bembi B, Cerini E, Danesino C et al. (2008) Management and treatment of glycogenosis type II. Neurology 71(23 Suppl 2):S12–S36
Burrow TA, Hopkin RJ, Leslie ND, Tinkle BT, Grabowski GA (2007) Enzyme reconstitution/replacement therapy for lysosomal storage diseases. Curr Opin Pediatr 19:628–635
Connock M, Burls A, Frew E et al. (2006) The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher's disease: a systematic review. Health Technol Assess 1(iii-iv):ix–136
DeRuisseau LR, Fuller DD, Qiu K et al. (2009) Neural deficits contribute to respiratory insufficiency in Pompe disease. Proc Natl Acad Sci USA 106:9419–9424
Enright PL, Sherrill DL (1998) Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med 158:1384–1387
Fukuda T, Ahearn M, Roberts A et al. (2006) Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol Ther 14:831–839
Geiger R, Strasak A, Treml B et al. (2007) Six-minute walk test in children and adolescents. J Pediatr 150:395–399
Hagemans ML, Winkel LP, Van Doorn PA et al. (2005) Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain 128(Pt 3):671–677
Joshi PR, Gläser D, Schmidt S et al. (2008) Molecular diagnosis of German patients with late-onset glycogen storage disease type II. J Inherit Metab Dis. doi:10.1007/s10545-008-0820-2
Kishnani PS, Nicolino M, Voit T et al. (2006) Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr 149:89–97
Lehmann EL (2006) Nonparametrics: statistical methods based on ranks, 2nd edn. Springer, New York
Merk T, Wibmer T, Schumann C, Krüger S (2009) Glycogen storage disease type II (Pompe disease)–influence of enzyme replacement therapy in adults. Eur J Neurol 16:274–277
Montalvo AL, Bembi B, Donnarumma M et al. (2006) Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. Hum Mutat 27:999–1006
Pellegrini N, Laforet P, Orlikowski D et al. (2005) Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease. Eur Respir J 26:1024–1031
Perez T (2006) Neuromuscular disorders—assessment of the respiratory muscles. Rev Neurol 162:437–444
Raben N, Lu N, Nagaraju K, Rivera Y et al. (2001) Conditional tissue-specific expression of the acid alpha-glucosidase (GAA) gene in the GAA knockout mice: implications for therapy. Hum Mol Genet 10:2039–2047
Ravaglia S, Moglia A, Costa A, Repetto A, Danesino C (2009) Enzyme replacement therapy in late-onset type II glycogenosis. Eur J Neurol 16:e125
Redelmeier DA, Bayoumi AM, Goldstein RS, Guyatt GH (1997) Interpreting small differences in functional status: the Six Minute Walk test in chronic lung disease patients. Am J Respir Crit Care Med 155:1278–1282
Rohrbach M, Clarke JT (2007) Treatment of lysosomal storage disorders: progress with enzyme replacement therapy. Drugs 67:2697–2716
Slonim AE, Bulone L, Goldberg T et al. (2007) Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy. Muscle Nerve 35:70–77
Steier J, Kaul S, Seymour J et al. (2007) The value of multiple tests for respiratory muscle strength. Thorax 62:975–980
Strothotte S, Strighl-Pill N, Grunert B et al. (2010) Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol 257:91–97
van den Hout JM, Kamphoven JH, Winkel LP et al. (2004) Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics 113:448–457
Van Der Laan P, Verdooren LR (1987) Classical analysis of variance methods and nonparametric counterparts. Biometr J 29(6):635–665
van der Ploeg AT, Reuser AJ (2008) Pompe's disease. Lancet 372:1342–1353
van der Ploeg AT, Clemens PR, Corzo D et al (2010) A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med 362:1396–1406
Winkel LP, Hagemans ML, van Doorn PA et al. (2005) The natural course of non-classic Pompe's disease; a review of 225 published cases. J Neurol 252:875–884
Zimran A, Bembi B, Pastores GM (2007) Enzyme replacement therapy for type I Gaucher disease. In: Futerman AH, Zimran A (eds) Gaucher disease. Taylor and Francis, New York, pp 341–354
Acknowledgments
This work was supported by the Agenzia Italiana del Farmaco (AIFA) D.G. 62229; by I.R.C.C.S. Burlo Garofolo-Trieste, RC 92/05; by a grant from “Programma Italia-USA”-526D/47 of the Istituto Superiore di Sanità, Rome; and by a grant from the Italian Association of Glycogenosis (AIG). The authors wish to thank the participating patients and their families for their precious contribution to data collection and clinical information and Sarah Tripepi Winteringham, MCIL, for her assistance in manuscript editing.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by: Ed Wraith
Competing interest: None declared.
Rights and permissions
About this article
Cite this article
Bembi, B., Pisa, F.E., Confalonieri, M. et al. Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. J Inherit Metab Dis 33, 727–735 (2010). https://doi.org/10.1007/s10545-010-9201-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-010-9201-8