Longitudinal evaluation of neurological and sensory changes in Gaucher disease: a prospective observational cohort study (SENOPRO)

Background: Gaucher disease (GD) is a rare lysosomal storage disorder caused by muta tions in the GBA1 gene. Traditionally, GD is classified into three subtypes based on the severity of neurological involvement; however, overlapping clinical features increasingly suggest a continuum of phenotypes rather than distinct categories. In this prospective observational cohort study, we conducted a multidisciplinary assessment of patients with GD to identify and monitor neurological, cognitive, auditory, and visual impairments. Materials and Methods: A comprehensive clinical and instrumental evaluation was per formed at baseline and repeated at follow-up, with a median interval of 37 months (IQR 36–38). Neurological assessments included physical examination, clinical rating scales, video-EEG, and brain MRI. Cognitive status was assessed using a standardized battery of neuropsychological tests. Detailed audiological and ophthalmological evaluations were also conducted. Paired parametric or non-parametric tests were applied as appropriate, with Bonferroni correction for cognitive outcomes (p < 0.05). Results: Of the 22 patients assessed at baseline, 18 completed the follow-up evaluation. Neurological assessments showed a worsening of subtle parkinsonian signs, with significant increases in Movement Disorder Society–Unified Parkinson’s Disease Rating Scale Part III scores (p = 0.04) and non-motor symptom scores (p = 0.01). Two of the eighteen patients developed epilepsy AcademicEditor: ChiKwanTsang Received: 23February2026 Revised: 30March2026 Accepted: 31March2026 Published: 2 April2026 Copyright: ©2026bytheauthors. Licensee MDPI,Basel,Switzerland. This article is an open access article distributed under the termsand conditions of the Creative Commons Attribution (CC BY)license. during follow-up. A high prevalence of sleep disturbances was confirmed, with 27.8% ex hibiting excessive daytime sleepiness and 16.7% reporting REM sleep behaviour disorder on standardized questionnaires. Compared with baseline, cognitive assessments revealed a higher proportion of patients with performance below normative population scores in at least one cognitive domain, particularly memory. Sensorineural hearing loss was confirmed in 11 of 15 patients (73.3%) who underwent audiological evaluation, with pro gressive worsening of audiometric thresholds observed in 7 of 11 (64%). Ophthalmological evaluations showed no changes in visual acuity or OCT findings; however, multifocal elec troretinography abnormalities were detected in 12 of 13 patients. Conclusions: Through in-depth phenotyping, this study identifies measurable neurological, cognitive, and sen sory progressive changes in patients with GD over time, supporting the value of tailored, multidisciplinary long-term care strategies to monitor and address emerging clinical needs in this rare disease