Gaucher Disease Type 1 Carries 12% Parkinson Risk by Age 80

Pathogenic variants in the glucocerebrosidase gene (GBA1) are the most common genetic risk factor for Parkinson disease, conferring an odds ratio of 5.43 for carriers compared to non-carriers [1, 2]. While biallelic GBA1 mutations cause Gaucher disease, a lysosomal storage disorder, even heterozygous carriers face a higher incidence of cognitive and motor dysfunction [3, 4]. This link is thought to involve a bidirectional mechanism where reduced glucocerebrosidase activity promotes the aggregation of alpha-synuclein, a key protein implicated in synucleinopathies [5, 6, 7]. Despite this established association, the lifetime penetrance of parkinsonism in patients with Gaucher disease has remained unclear. A new longitudinal analysis of 1,618 patients from a global registry provides greater clarity, reporting an age-specific Parkinson disease prevalence of 12.2% by age 80 [8].