Objective: To evaluate whether there are distinct motor and non-motor symptom characteristics in GBA-associated PD (GBA-PD) in a Greek population.

Background: Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GCase) have been reported to lead to a more severe PD phenotype, in particular higher prevalence of cognitive impairment and earlier age at onset, compared to non-mutation carriers. Additional genotype-phenotype correlations have suggested that the phenotype may also depend on the particular GBA1 mutation.

Methods: Thirty three patients with GBA-PD were compared to 33 with sporadic PD (sPD). Within GBA-PD, we also categorized patients in 3 subgroups with the most frequent GBA1 mutations (11 D409H, 12 L444P, 8 N370S). The two groups were matched for sex, disease duration and age. We assessed motor impairment with UPDRS III. Modified H&Y and Schwab and England Activities of Daily Living scales were also used. A predefined questionnaire was used concerning demographic data, unilateral or bilateral as first side affected, and the presence of dementia, autonomic dysfunction, psychosis and depression. Cognitive dysfunction was tested using sMMSE. The Mann Whitney U test was performed for the comparison between GBA and sPD and the Kruskal Wallis H-test for the GBA subgroups. Dichotomous data were analyzed using the Chi-square test.

Results: Cognitive impairment was more severe in GBA-PD vs sPD according to the sMMSE (p<0.05) and the questionnaire for the presence of dementia (p<0.05). Additionally, bilateral presentation was significantly more frequent in GBA-PD than in sPD (p<0.05). As for GBA subgroup comparisons, no significant differences were found, possibly because of the small numbers within each subgroup.

Conclusions: Our results confirm, in a Greek population, previously reported higher prevalence of cognitive impairment in GBA-PD vs sPD, but also reveal the less acknowledged feature of a higher frequency of bilateral onset of the disease in GBA1 mutation carriers. Whether these two features of GBA-PD are inter-related will require further study. Such concepts may aid in patient stratification, prognosis and eventually specific therapeutic interventions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-characteristics-in-gba-associated-parkinsons-disease-pd-a-study-in-a-greek-population/