Abstract Details

Title Age-specific Risk of Parkinson’s Disease and Parkinsonian Syndrome in Patients with Type 1 Gaucher Disease: Real-world Evidence from the International Collaborative Gaucher Group Gaucher Registry

Topic Movement Disorders

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-001

Objective To estimate the risk of Parkinson’s disease (PD) using Kaplan-Meier survival curves, and to estimate relative hazards of PD using Cox proportional hazards models adjusted for age (as time scale), sex, glucocerebrosidase (GBA1) genotype category (mild versus severe mutations), and disease severity (history of bone crisis).

Background GBA1 gene mutations are the most common risk factor for PD; however, there is insufficient data on the age-specific risk for PD among biallelic GBA1 mutations carriers with type 1 Gaucher disease (GD1). These data are essential for counseling and identification of risk modifiers.

Design/Methods Participants were GD1 patients enrolled in the International Collaborative Gaucher Group Gaucher Registry as of August 4, 2023. We collected data on occurrence of clinical diagnosis of PD and motor (e.g., rest tremor, falls) and non-motor (cognitive impairment, REM sleep behavior disorder, loss of sense of smell, autonomic dysfunction) signs often present in parkinsonian syndrome. To not miss patients not yet formally diagnosed with PD, dementia with Lewy bodies (DLB), or prodromal PD/DLB, we defined possible parkinsonian syndrome based on self-reported signs and symptoms (data not shown).

Results

Overall, 39 of 1,452 patients were diagnosed with PD. Sex (p=0.93) and disease severity (p=0.82) were not associated with risk of PD. Overall, age-specific risk for PD was 3.3% at age 60 and 11.8% at age 80 years. Among patients with genotype data (N=1,376), N370S homozygotes had a lower risk for PD than patients with 1 or 0 N370S variants (at age 60 years, 1.9%, 3.4%, 9.1% respectively; at age 80 years, 11.5%, 10.8%, and 23.3%).

Conclusions

We provide age-specific risk for PD in the largest GD1 cohort studied to date. Risk was highest for patients with severe GBA1 mutations. While risk is higher than the general population, we estimated that most GD1 patients will not develop PD by age 80.

Authors/Disclosures
Alessio D. Di Fonzo (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico) PRESENTER	No disclosure on file
Roy Alcalay, MD (Columbia University)	Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.
Pramod Mistry (Yale University)	No disclosure on file
JULIE BATISTA (Sanofi)	No disclosure on file
Pablo Bianculli (Sanofi)	No disclosure on file
Jenny Carwile	No disclosure on file
Maria Perichon (Sanofi)	No disclosure on file
Manisha Balwani	No disclosure on file

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