Longitudinal Motor Function Changes in Adults With Late-Onset Pompe Disease: Key Determinants and Clinical Thresholds

Late-onset Pompe disease (LOPD) causes progressive muscle weakness, locomotor dysfunction, and postural instability, severely affecting quality of life. Longitudinal data on these changes remain limited. We quantified changes in muscle strength, locomotor performance, and postural control in adults with LOPD vs controls, aiming to identify the most sensitive motor parameters and determine key muscle contributors to locomotor and postural decline. We also defined clinically meaningful thresholds (minimal clinically important difference [MCID]) for sensitive parameters in LOPD.

This longitudinal study evaluated motor functions over 2 years using instrumented and clinical assessments of lower limb strength, gait (performance and spatiotemporal parameters), and standing postural control (stability and orientation). Responsiveness was analyzed with effect size (α) after significance and with standardized response mean (SRM). Clinically meaningful changes were highlighted using MCID. Stepwise regressions identified key muscle predictors of locomotor and postural decline.

Forty participants were included (20 with LOPD, 20 controls; mean age 58.0 ± 12.8 and 58.1 ± 9.1 years, respectively; 50% women). After 2 years, deterioration in participants with LOPD was observed in hip extensor and abductor strength, knee flexor strength, ankle plantar flexor strength, walking speed, single-limb stance gait phase, and postural sway velocity (all p < 0.009). While manual muscular testing showed no significant change, the most sensitive-to-change parameters were hip extensor and abductor strength assessed with a dynamometer and walking speed (α > 0.55; SRM > 0.75). The highest proportion of patients exceeding the MCID over 2 years was observed for hip abductor strength, ankle plantar flexor strength, and single-limb stance gait phase.

Our results found significant deterioration in motor parameters in adults with LOPD. Hip muscle deterioration contributes directly to gait and stability decline while plantar flexors play a pivotal role in maintaining cautious gait and balance. The aim of this study was to identify sensitive-to-change parameters and MCID thresholds to provide clinicians with meaningful benchmarks to guide evaluations and interventions. Hip extensor and abductor strength (dynamometer) and walking speed emerged as the most responsive parameters, recommended for monitoring disease progression, optimizing rehabilitation, and assessing emerging treatments. Further studies are needed to confirm these findings in broader LOPD populations and evaluate treatment effects over longer periods.