Disease Progression of GNE Myopathy and Its Relationship With Genotype: A Retrospective, Observational Study in Chinese Patients.

Background and objectives: Studies on the natural disease progression of detailed motor dysfunction in patients with GNE myopathy are rare. This study aimed to investigate motor function involvement during disease progression and its relationship with the genotype among Chinese patients with GNE myopathy.

Methods: This retrospective observational cohort study included all patients with genetically confirmed GNE myopathy enrolled at Peking University First Hospital between 2000 and 2023. Patients with GNE myopathy were stratified into 2 subgroups based on with or without p.D207V mutation. Data on clinically significant muscular problems were collected from patients' medical history and follow-up assessments to evaluate motor function using the GNE Myopathy Functional Activity Scale and the modified Rankin Scale.

Results: Eighty-three patients with GNE myopathy were included, with a median age at examination of 36 years (range 25-57) and a median age at onset (AAO) of 26 years (range 16-46). The Kaplan-Meier curves revealed that patients with the p.D207V mutation experienced a significantly later AAO (27 years [95% CI 25-29]) and onset age of wheelchair dependency (50 years [95% CI 46-54]) compared with those without the mutation, who had an AAO of 24 years (95% CI 22-26) and an onset age of wheelchair dependency of 45 years (95% CI 36-54). Multivariate Cox regression analysis, adjusted for sex and disease duration, revealed that patients without the p.D207V mutation had a higher risk of wheelchair dependency, with an adjusted hazard ratio of 2.361 (95% CI 1.030-5.411). Barthel indexes (BIs) were negatively correlated with the disease duration and positively correlated with AAOs. Patients with GNE with earlier AAO exhibited a shorter disease duration of developing functional dependency (BIs <60) than did those with later AAOs.

Discussion: Our results provide insights into the motor function involvement observed during disease progression in Chinese patients with GNE myopathy, and relatively mild disease severity was observed in those with the p.D207V mutation.