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

Area of Science:

• Neurology
• Movement Disorders
• Clinical Research

Background:

• Late-onset Pompe disease (LOPD) is a progressive neuromuscular disorder causing significant muscle weakness and functional decline.
• Limited longitudinal data exist on the progression of motor deficits in adults with LOPD.
• LOPD severely impacts quality of life due to muscle weakness, gait impairment, and postural instability.

Purpose of the Study:

• To quantify changes in muscle strength, gait, and postural control in adults with LOPD over two years.
• To identify the most sensitive motor parameters for tracking LOPD progression.
• To define minimal clinically important difference (MCID) thresholds for key LOPD-related motor parameters.

Main Methods:

• A 2-year longitudinal study involving 20 adults with LOPD and 20 age-matched controls.
• Instrumented and clinical assessments of lower limb strength, gait (spatiotemporal parameters, performance), and postural control (sway velocity, stability).
• Analysis of parameter responsiveness using effect size (α) and standardized response mean (SRM), with MCID defined for clinically meaningful changes.

Main Results:

• Participants with LOPD showed significant deterioration in hip extensor/abductor strength, knee flexor strength, ankle plantar flexor strength, walking speed, and postural sway velocity over two years (p < 0.009).
• Dynamometer-measured hip abductor/extensor strength and walking speed were the most sensitive parameters to change (α > 0.55, SRM > 0.75).
• Hip abductor strength, ankle plantar flexor strength, and single-limb stance duration exceeded MCID in the highest proportion of LOPD patients.

Conclusions:

• Adults with LOPD experience significant motor deterioration over two years, with hip muscle weakness directly impacting gait and stability.
• Ankle plantar flexors are crucial for maintaining cautious gait and balance in LOPD.
• Hip extensor/abductor strength and walking speed are recommended as sensitive biomarkers for monitoring LOPD progression and evaluating interventions.