Abstract
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.
Highlights
Pompe disease (PD) is a rare, inheritable, multisystemic lysosomal storage disorder caused by a deficiency of acid alpha-glucosidase (GAA), which leads to accumulation of glycogen within lysosomes, especially in the heart, skeletal and smooth muscles, and in the nervous system [1, 2]
The search strategy was developed with the following keywords: Pompe disease, alpha glucosidase deficiency, acid maltase deficiency, glycogen storage disease type 2, enzymatic replacement therapy, enzyme replacement therapy, forced vital capacity, FVC, respiratory function, six-minute walk test, 6-min walk test (6MWT), medical research council, MRC, quantitative muscle testing, QMT, quick motor function test, QMFT
A total of 16 studies were included in the meta-analysis, containing clinical data from 589 patients with late-onset Pompe disease (LOPD) [1, 7, 16–29]
Summary
Pompe disease (PD) is a rare, inheritable, multisystemic lysosomal storage disorder caused by a deficiency of acid alpha-glucosidase (GAA), which leads to accumulation of glycogen within lysosomes, especially in the heart, skeletal and smooth muscles, and in the nervous system [1, 2]. LOPD, is clinically more heterogeneous [5], involving primarily skeletal and respiratory muscles leading to proximal weakness and respiratory insufficiency typically without cardiac manifestations [2, 5]. Available from: https://www.wiley.com/en-us/Introduction+to+Meta+Analysis-p-9780470057247 (accessed 7 Oct 2020). Ravaglia S, Pichiecchio A, Ponzio M, Danesino C, Saeidi Garaghani K, Poloni GU et al (2010) Changes in skeletal muscle qualities during enzyme replacement therapy in late-onset type II glycogenosis: temporal and spatial pattern of mass vs strength response. Strothotte S, Strigl-Pill N, Grunert B, Kornblum C, Eger K, Wessig C 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.
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