A benign course of Parkinson's disease associated with different mutations in the glucocerebrosidase gene - A case series

Mikhal E Cohen; Yosef Shechter; Roni Eichel; Gilad Yahalom

doi:10.1016/j.parkreldis.2024.106990

A benign course of Parkinson's disease associated with different mutations in the glucocerebrosidase gene - A case series

Parkinsonism Relat Disord. 2024 May 4:124:106990. doi: 10.1016/j.parkreldis.2024.106990. Online ahead of print.

Authors

Mikhal E Cohen¹, Yosef Shechter², Roni Eichel³, Gilad Yahalom²

Affiliations

¹ Department of Neurology, Shaare Zedek Medical Center and School of Medicine, The Hebrew University, Jerusalem, Israel; The Movement Disorders Unit, Shaare Zedek Medical Center, Jerusalem, Israel. Electronic address: mikhalc@szmc.org.il.
² Department of Neurology, Shaare Zedek Medical Center and School of Medicine, The Hebrew University, Jerusalem, Israel; The Movement Disorders Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
³ Department of Neurology, Shaare Zedek Medical Center and School of Medicine, The Hebrew University, Jerusalem, Israel.

PMID: 38735164
DOI: 10.1016/j.parkreldis.2024.106990

Abstract

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-PD), and compared them to the other regular GBA-PD group (rGBA-PD) and to mutation negative patients (MNP).

Methods: All patients who performed next generation testing were enrolled. We defined bGBA-PD 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-PD group to the rGBA-PD 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-PD. Seventeen patients were LRRK2-PD and 123 patients were MNP. The rate of Rapide Eye Movement Behavioral Disorder (RBD) was highest in the rGBA-PD group and lowest in the bGBA-PD group (100 % vs. 28.6 %) (p < 0.001). The bGBA-PD group scored significantly higher in the Montreal Cognitive Assessment (MoCA) than rGBA-PD 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-PD.

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.