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

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.

Keywords: 6MWD; Biodex® dynamometer; ERT; GSD2; LOPD; enzyme replacement therapy; glycogen storage disease type 2; isometric; longitudinal; muscle strength.

Figure 1

Isometric muscle strength results using Biodex^® in knee extensors and 6MWD in patients and controls. Results of the mean isometric muscle strength (±1 standard deviation, SD) in Newton meters (Nm) of the left (A) and right (B) knee extensors measured using the Biodex^® dynamometer are shown for LOPD patients (black) and controls (gray) for the study duration of 24 months. In (C), the mean 6MWD (±1 standard deviation, SD) in meters (m) is presented for patients (black) and control individuals (gray) for the study duration of 24 months. In (D), the mean 6MWD (±1 standard deviation, SD) in meters (m) is presented for patients with non-invasive ventilation (NIV) (black) and those without NIV (gray). In panels (A–C), an asterisk (*) indicates a significant difference with the baseline value (0 months).