Objective: The aim of our study was to determine the prevalence and clinical characteristics of Slovak GBA-related patients with Parkinson’s disease (PwP).

Background: GBA variants have been established as a significant risk factor for Parkinson’s disease (PD) [1]. Extensive research has highlighted distinctive clinical features of GBA-associated PD [2], although the exact prevalence and clinical phenotype of GBA-related PD in the Slovak population has not been precisely determined.

Method: In a routine diagnostic setting, the GBA variants were analyzed using an amplicon-based next-generation sequencing technique. In subjects with detected GBA variants, in-depth phenotyping was performed using standardized questionnaires and scales.

Results: GBA variants were identified in 20/378 of PwPs (5.29%) in our study, with the most prevalent being p.(Asn409Ser) in 7 patients, p.(Gly416Ser) in 4 patients, and p.(Leu483Pro) in 2 patients. Twelve subjects (60%) were men, mean age was 66.5±9.5 years, 25% had a positive family history of PD. Age of onset of GBA-positive (GBA+) PwPs was 56.6±11.3 years compared to 61.1±10.4 in those without GBA variants. The majority of subjects (15/20) showed a mixed PD phenotype, with a mean MDS-UPDRS score of 36±12.4 points. All GBA+ patients complained of non-motor symptoms. Of 14 subjects with available formal cognitive testing, 9 presented with PD-dementia, while 2 presented with PD-mild cognitive impairment (78.57% in total). Hallucinations were reported by 7/20 (35%) GBA+ subjects, compared to 6.8% in those without GBA variants. All GBA+ patients complained of non-motor symptoms, specifically sleep problems (14/20), fatigue (6/20), excessive daytime sleepiness (6/20); mood disorders (13/20); urinary problems (8/20) and constipation (10/20). A minority of GBA+ patients reported RBD (7/20), 3 patients complained of loss of smell.

Conclusion: GBA heterozygous variants are prevalent in Slovak PwPs. The clinical characteristics of GBA+ PD resemble those of idiopathic PD, although patients with GBA-parkinsonism in our cohort have an increased likelihood of cognitive impairment and a lower average age of onset. Identification of GBA variant carriers is crucial as novel treatment option for GBA-related PD are emerging in clinical trials.

References: [1] Sidransky, Ellen, a Grisel Lopez. “The Link between the GBA Gene and Parkinsonism”. The Lancet Neurology, roč. 11, č. 11, november 2012, s. 986–98. DOI.org (Crossref), doi:10.1016/S1474-4422(12)70190-4.
[2] Zhang Y, Shu L, Zhou X, Pan H, Xu Q, Guo J, Tang B, Sun Q. A Meta-Analysis of GBA-Related Clinical Symptoms in Parkinson’s Disease. Parkinsons Dis. 2018 Sep 27;2018:3136415. doi: 10.1155/2018/3136415. PMID: 30363648; PMCID: PMC6180987.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-prevalence-and-clinical-features-of-gba-related-parkinsons-disease-in-a-slovak-patient-cohort/