Clinical course and biomarkers in patients with type 1 Gaucher disease and Parkinson's disease: A retrospective cohort study

Introduction Pathogenic variants in GBA1 , the gene encoding beta-glucocerebrosidase, are significant genetic risk factors for Parkinson's disease (PD). Patients with type 1 Gaucher disease (GD1), caused by biallelic GBA1 variants, have approximately six-fold higher lifetime risk for PD compared to the general population. However, few studies have described the clinical presentation of GD-associated PD (GD-PD) in GD1 patients. We describe the variable presentation of PD and evaluate clinical characteristics and biomarkers in a cohort of patients with concurrent diagnoses of GD-PD. Methods Retrospective case-control analysis of GD1 patients within a single academic clinic from 2010 to 2020 comparing against age- and sex-matched controls. Results Among eleven patients diagnosed with GD-PD, the median age of GD1 diagnosis was 33 years (interquartile range/IQR 28–54 years), and all were on treatment with enzyme replacement therapy ( n = 8, 72.7%) or substrate reduction therapy ( n = 3, 27.3%) at follow-up. The average age of onset of PD symptoms was 54.6 years old with a median age of onset of 53 years old (IQR 47–59) and four patients developing symptoms before the age of 50. The majority ( n = 9, 81.8%) were treated with levodopa/carbidopa with or without deep brain stimulation. Within this limited cohort, neither clinical phenotype nor systemic GD biomarkers distinguished GD-PD cases from controls. Conclusions Data from this single-center cohort demonstrate considerable variability in GD-PD among GD1 individuals and suggest that GD1 patients may have increased risk of GD-PD before the age of 50. Routine screening for PD in GD1 patients starting at age 40 may aid early diagnosis and close monitoring for initiation of PD-directed treatment.