Prevalence and Severity of Non-motor Manifestations in Patients with Gaucher Disease and Heterozygous GBA1 Mutation Carriers (P2.143)

Objective: To identify the prevalence and severity of non-motor symptoms in a group of patients at risk for developing Parkinson disease (PD). Background: The link between mutations in the glucocerebrosidase gene (GBA1) and the risk for the development of parkinsonism is well-established in the literature. The prevalence of non-motor symptoms associated with sporadic PD that may be present years before motor manifestations has not been explored in subjects affected with Gaucher disease or carrying heterozygous GBA1 mutations without clinical evidence of parkinsonism. Design/Methods: Patients with Gaucher disease or heterozygous mutation carriers with a family history of Parkinson disease were longitudinally evaluated at the National Institutes of Health, National Human Genome Research Institute Genetics clinic. A series of validated scales assessing depression, fatigue, restless legs symptoms, olfactory function, anxiety, and cognition were administered during their evaluation. Complete physical and neurological evaluations were done to confirm the absence of parkinsonian motor features. Results: Sleep disturbances were more frequently reported by patients with Gaucher disease and heterozygous mutation carriers compared to unaffected individuals, but less frequently than by patients with parkinsonism. Interestingly, anxiety scores were higher in subjects with Gaucher Disease and mutation carriers than in those with Gaucher disease or mutation carriers who also had Parkinsonian symptoms. Conclusions: Continued longitudinal evaluation of patients with Gaucher disease and heterozygous carriers of GBA1 mutations may help identify a pre-motor phase in this cohort at risk of developing parkinsonism. This pre-motor profile may suggest specific neurotransmitters involved in neurodegeneration and contribute to a better understanding of the association between lysosomal dysfunction and alpha-synuclein aggregation. Disclosure: Dr. Kim has nothing to disclose. Dr. Cintron has nothing to disclose. Dr. Wiggs has nothing to disclose. Dr. Groden has nothing to disclose. Dr. Sidransky has nothing to disclose. Dr. Lopez has nothing to disclose.