Six-Minute Walk Distance Is a Useful Outcome Measure to Detect Motor Decline in Treated Late-Onset Pompe Disease Patients.

Kristl G Claeys,Lucas Fache,Koen Peers,Christophe E Depuydt,Ann D’Hondt

doi:10.3390/cells11030334

Abstract

Late-onset Pompe disease (LOPD) is a rare, progressive disorder characterized by limb–girdle muscle weakness and/or respiratory insufficiency, caused by acid alpha-glucosidase (GAA) gene mutations and treated with enzyme replacement therapy. We studied isometric muscle strength in eight muscle groups bilaterally using a Biodex® dynamometer, as well as the Medical Research Council sum score (MRC-SS), hand grip strength, 6 min walk distance (6MWD), 10 m walk test (10MWT) and timed up-and-go test (TUG) in 12 adult, ambulatory, treated LOPD patients and 12 age-/gender-matched healthy controls, every 6 months for 2 years. The mean isometric muscle strength showed a significant decline in right and left knee extensors at 12 months in controls (p < 0.014; p < 0.016), at 18 months in patients (p < 0.010; p < 0.007) and controls (only right side, p < 0.030) and at 24 months in both groups (p < 0.035). The mean 6MWD in patients significantly decreased after 24 months, from 451.9 m to 368.1 m (p < 0.003), whereas in controls, the mean 6MWD significantly increased after 6 months (p < 0.045) and 18 months (p < 0.020) (at 24 months p = 0.054). In patients and controls, the MRC-SS, hand grip test, 10MWT and TUG did not show significant changes (p > 0.05). We conclude that the 6MWD is a useful outcome measure to detect motor decline in treated LOPD patients.

Highlights

Late-onset Pompe disease (LOPD; known as glycogen storage disease type 2 or GSD2) is a rare autosomal recessive disorder caused by acid alpha-glucosidase (GAA) deficiency
Results of Biodex® Dynamometer and Other Outcome Measures in LOPD Patients In LOPD patients, the mean isometric muscle strength measured using a Biodex® dynamometer showed a significant deterioration in the knee extensors bilaterally at 18 months and 24 months compared to baseline (Table 2; Figure 1A,B)
There were no significant differences between the means at the different visits (V1–V5) for each of the outcome measures in LOPD patients (ANOVA, p > 0.05; Table 2)

Summary

Introduction

Late-onset Pompe disease (LOPD; known as glycogen storage disease type 2 or GSD2) is a rare autosomal recessive disorder caused by acid alpha-glucosidase (GAA) deficiency. In previous studies showing the effect of ERT in LOPD patients, the 6 min walk distance test (6MWD) was mainly used as a consistent positive outcome measure of motor function in this disease [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24]. Motor strength as an outcome measure using the manual Medical Research Council sum score (MRC-SS) showed inconsistent results, with a significant improvement in ERT-treated LOPD patients in some studies [17,21], but without amelioration in others [9,15]. The Biodex® dynamometer has been introduced in the neuromuscular field to assess muscle strength in an objective, quantitative manner, in patients with Duchenne muscular dystrophy [25], hereditary inclusion body myopathy [26] and in a small study with four treated LOPD patients [18]

Methods

Results

Conclusion