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Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

Juna M de Vries12, Nadine AME van der Beek12, Wim CJ Hop3, Francois PJ Karstens4, John H Wokke5, Marianne de Visser6, Baziel GM van Engelen7, Jan BM Kuks8, Anneke J van der Kooi6, Nicolette C Notermans5, Catharina G Faber9, Jan JGM Verschuuren10, Michelle E Kruijshaar2, Arnold JJ Reuser11, Pieter A van Doorn1 and Ans T van der Ploeg2*

Author Affiliations

1 Department of Neurology & Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands

2 Department of Pediatrics & Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands

3 Department of Epidemiology and Biostatistics, Erasmus MC University Medical Center, Rotterdam, the Netherlands

4 Department of Internal Medicine & Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands

5 Department of Neurology, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Utrecht, the Netherlands

6 Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands

7 Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

8 Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands

9 Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands

10 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

11 Department of Clinical Genetics & Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands

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Orphanet Journal of Rare Diseases 2012, 7:73  doi:10.1186/1750-1172-7-73

Published: 26 September 2012

Abstract

Background

Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors.

Methods

Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

Results

Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (−1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.

Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC.

Conclusions

We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

Keywords:
Pompe disease; Glycogen storage disease type II; OMIM number 232300; Acid α-glucosidase; Alglucosidase alfa; Enzyme replacement therapy; Lysosomal storage disorder; Muscle strength; Lung function