Prospective gait analysis in patients from the French registry of glycogen storage disease type III: implications for clinical trials

BACKGROUND AND OBJECTIVES: Glycogen storage disease type III (GSD-III) is a genetic metabolic disorder affecting liver and muscle, frequently leading to walking difficulties in adults. This study aimed to quantify walking performance and its progression in GSD-III, identify relevant outcome measures for future clinical trials, and determine predictors of gait decline. METHODS: Participants enrolled in the French GSD-III registry underwent an annual assessment of their 6-min walk distance (6MWD) combined with 3D trunk accelerometry. Muscle strength for flexion and extension of the knee and ankle, as well as Motor Function Measure (MFM) scores, were also collected. RESULTS: Among registry participants, 93% were ambulant without assistance. The 6MWD of participants with GSD-III (n = 46, aged 10-49 years) was lower than that of controls (n = 53) (adjusted p < 0.001), due to reduced stride frequency and stride length/height ratio (adjusted p < 0.001). Accelerometry revealed no abnormalities beyond those related to slower walking speed. 6MWD correlated with muscle strength and accelerometry variables. In adults, total MFM score declined with age (adjusted p < 0.001), whereas 6MWD remained stable overall, despite a gradual decline in a few patients. Preliminary models suggest that lower baseline MFM sub-scores and specific trunk accelerometry variables may predict 6MWD deterioration. DISCUSSION: The walking impairment remains stable in most patients. MFM sub-scores and accelerometry variables may help identify the rare individuals at risk of gait decline. Unlike 6MWD, total MFM score worsened in adulthood and appears to be the most relevant muscle outcome measure for future clinical trials in GSD-III. FRENCH GSD-III REGISTRY REGISTRATION NUMBER: NCT06616545 was retrospectively registered on 27 SEP 2024.