Objective: To estimate the age-specific risk of Parkinson’s disease (PD) and possible parkinsonian syndrome (pPS) in Gaucher disease (GD) based on registry data.

Background: While both heterozygous and biallelic mutations in GBA1 are established risk factors for PD, little is known about the age-specific risk for PD among type 1 GD (GD1) patients with biallelic GBA1 mutation. Such data are important for providing patient guidance and identifying risk-modifiers.

Method: The International Collaborative Gaucher Group (ICGG) Gaucher Registry collects data on Gaucher patients at ∼280 sites across 64 countries. We collected PD-related data, including clinical diagnosis of PD and dementia with Lewy bodies (DLB) and report of motor signs/symptoms (e.g., falls, rest tremor) and non-motor signs/symptoms (e.g., REM sleep behavior disorder, cognitive impairment, autonomic dysfunction, loss of sense of smell) related to PD. We defined a conservative diagnosis of PD based on clinical diagnosis, and a more liberal diagnosis of pPS based on the presence of ≥2 signs/symptoms related to PD, or a diagnosis of PD or DLB, whichever occurred first. We estimated the age-specific risk of PD and pPS in GD1 patients overall and by GBA1 genotype category (mild variant [N409S or R535H] homozygotes vs. compound heterozygotes) using Kaplan-Meier survival curves and estimated relative hazards of PD and pPS by genotype category using Cox proportional models.

Results: Of 1,618 patients evaluated, 51 had PD and 78 had pPS [table1]. The overall prevalence (95% CI) of PD and pPS was 4.0% (2.7, 5.7) and 5.4% (4.0, 7.4), respectively, at 60 years and 12.2% (8.6, 17.0) and 20.6% (15.2, 27.6), respectively, at 80 years [table2, figures1-2]. Among 1,381 GD1 patients with ≥1 mild GBA1 variant, mild variant homozygotes had a lower prevalence of PD and pPS than compound heterozygotes across follow-up [table2]. Consistent findings were noted from Cox models (data not shown).

Conclusion: We estimated PD and pPS prevalence by age in the largest GD1 cohort assessed to date. While markedly higher than non-carriers’ risk for PD, most GD1 patients escape PD or pPS diagnosis based on our findings. These results highlight the importance of identifying early biomarkers and investigating genetic and environmental modifiers of PD risk in GD1 patients with homozygous or compound heterozygous GBA1 mutation.

Table 1

Table 2

Figure 1

Figure 2

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-parkinsons-disease-and-possible-parkinsonian-syndrome-in-gaucher-disease-data-from-the-icgg-gaucher-registry/