Objective: To describe a subtype of GBA-associated Parkinson’s disease with a benign motor and cognitive course of disease.

Background: Subjects carrying mutations in the GBA gene, whether in one or two alleles pose a risk to develop Parkinson’s disease (PD). This type of GBA-related PD has usually a severe course, and patients tend to develop cognitive deficits faster. Herein we describe 8 cases of GBA-PD patients with a markedly benign course (bGBA), and compared them to the other regular GBA-PD group (rGBA) and to mutation negative patients (MNP).Subjects carrying mutations in the GBA gene, whether in one or two alleles pose a risk to develop Parkinson’s disease (PD). This type of GBA-related PD has usually a severe course, and patients tend to develop cognitive deficits faster. Herein we describe 8 cases of GBA-PD patients with a markedly benign course (bGBA), and compared them to the other regular GBA-PD group (rGBA) and to mutation negative patients (MNP).

Method: All patients who performed next generation testing were enrolled. We defined bGBA as patients with disease duration of at least 5 years, with Hoehn and Yahr (HY) ≤3 and MoCA score of ≥24. Following a selection of patients with a disease duration of 3 years or longer up to 15 years or shorter, we compared the bGBA group to the rGBA and MNP in terms of demographic and clinical features.

Results: 166 patients (58 males) diagnosed with PD were genotyped. Twenty-five patients were GBA-PD, of whom 7 were defined as bGBA. Seventeen patients were LRRK2-PD and 123 patients were MNP. The rate of Rapide Eye Movement Behavioral Disorder (RBD) was highest in the rGBA group and lowest in the bGBA group (100% vs. 28.6%) (p<0.001). The bGBA group scored significantly higher in the MOntreal Cognitive Assessment (MoCA) than rGBA and MNP (27.6±2.0 vs. 19.8±3.9 vs. 23.5±3.7, respectively; p=0.006). There were no significant differences in MDS-UPDRS part-3 among the groups. There was no specific GBA mutation which was more commonly associated with bGBA.

Conclusion: While GBA-PD has a severe course of disease, a subgroup of which shows a benign course with a relatively preserved cognitive function even years after onset. We might suggest that these cases have other pathomechanism leading to PD, including an incidental GBA carriership.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-benign-course-of-parkinsons-disease-associated-with-different-mutations-in-the-glucocerebrosidase-gba-gene-a-case-series/