Clinical efficacy of the enzyme replacement therapy in patients with late-onset Pompe disease: a systematic review and a meta-analysis

J Neurol. 2022 Feb;269(2):733-741. doi: 10.1007/s00415-021-10526-5. Epub 2021 Apr 13.


In patients with late-onset Pompe disease (LOPD), the efficacy of the enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) is difficult to evaluate, due to the clinical heterogeneity and the small sample sizes in published studies. Therefore, we conduct a systematic literature review and meta-analysis of the literature to evaluate the efficacy of ERT in LOPD patients considering the walking distance, respiratory function and muscle strength. Particularly, six-minute walk test (6MWT), forced vital capacity (FVC), medical research council (MRC) grading, quantitative muscle testing (QMT), and quick motor function test (QMFT) were outcomes of interest. Overall, 619 studies were identified in PubMed, EMBASE and by manual search on July 18th, 2020. After an initial assessment, 16 studies were included in the meta-analysis, containing clinical data from 589 patients with LOPD. For the 6MWT, 419 patients were analyzed. Walking distance improved on average, 32.2 m greater during the observed period (p = 0.0003), compared to the distance at the baseline. The meta-analysis did not show any improvement in FVC and only a tendency towards better muscle strength after treatment with ERT, but the difference was not statistically significant. In conclusion, the available data showed that ERT has a significant beneficial efficacy in the improvement of walking distance in LOPD patients and a non-significant improvement of muscle strength. No improvement in respiratory capacity was found. More prospective and controlled trials are needed to demonstrate a clear clinical benefit of ERT.

Keywords: Enzyme replacement therapy; Gycogen storage disease type II; Late-onset Pompe disease; Meta-analyse; Pompe disease; Recombinant human alpha-glucosidase; Systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Enzyme Replacement Therapy
  • Glycogen Storage Disease Type II* / drug therapy
  • Humans
  • Prospective Studies
  • Treatment Outcome
  • alpha-Glucosidases / therapeutic use


  • alpha-Glucosidases