Effect of the enzyme replacement therapy on clinical outcomes in patients with late-onset Pompe disease: a systematic review

Abstract

Introduction: Pompe disease (PD) is a rare glycogen storage disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase, which affects approximately one every 40’000 people. Late onset Pompe disease (LOPD) is a particular and heterogeneous clinical form of Pompe disease whose symptoms appear after the first year of life. LOPD is characterized by progressive skeletal myopathy, followed by respiratory muscle weakness. Without treatment, LOPD leads typically to an early death. Since 2006, PD can be treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA). However, the long-term effect of ERT in patients with LOPD remains so far not completely understood. The objective of this study is to provide a systematic review on the effectiveness of ERT in patients with LOPD concerning respiratory function, motor performance, and muscle strength. Methods: On July 18th, 2020 614 studies were systematically identified in the electronic databases PubMed and EMBASE. Outcomes of interest were: respiratory function, as assessed by the forced vital capacity (FVC); motor performance, as measured by the 6-min walk test (6MWT); and muscle strength, as tested with the medical research council grading (MRC), quantitative muscles testing (QMT) or quick motor function test (QMFT). Results: Overall, 16 studies containing clinical data from 589 patients with LOPD were included in the systematic review. Studies included were published between 2010 and 2020. Our findings show that in patients with LOPD treated with ERT, compared to their baseline values before initiation of the treatment, the walking distance improved in 13 of 14 studies (92.85%) as assessed by the 6MWT, the muscle strength improved in 7 of 10 studies (70%), and the FVC improved in 8 of 16 studies (50%). Conclusions: Our systematic review shows that most of the studies in patients with LOPD had a beneficial effect on improving motor performance and muscle strength after initiation of the ERT. However, only half of the studies included showed an improvement of the respiratory function. New meta-analyses are needed to correlate the findings of the studies considering the different observation times.