Objective: To examine the occurrence of medical comorbidities associated with genetic form of Parkinson’s disease (GBA1-PD and LRRK2-PD) compared to a cohort of non-mutated PD (NM-PD), focusing on early detectable or treatable diseases.

Background: The most frequent cause of monogenic PD is pathogenic variant in LRRK2  gene, while GBA1 is considered as the main genetic risk factor for PD [1].

Method: This retrospective observational study included PD patients carrying pathogenetic variants in LRRK2 or GBA1 genes, and patients non-mutated in PD-associated genes (NM-PD) as control group. We collected demographic data and the following personal comorbidities (presence/absence): cardiological, oncological, cerebrovascular, kidney, endocrinological, autoimmune and immuno-mediated diseases, aneurysms or arteriovenous malformations, type 2 Diabetes Mellitus (T2-DM) and dyslipidemia. Categorical variables were reported as percentages, while continuous variables as medians and interquartile range. Fisher exact test was used to compare comorbidities’ prevalence between groups.

Results: 165 PD patients were included: 73 GBA1-PD (male: 52; age: 69 years; disease duration: 10.5 years), 23 LRRK2-PD (male: 12; age: 63 years; disease duration:10 years) and 69 NM-PD (male: 44; age: 64 years; disease duration: 8 years). LRRK2-PD patients had a significantly greater prevalence of oncological disease, compared to NM-PD (39.13% vs 11.59%, p=0.01), but not compared to GBA1-PD (39.13% vs 20.55%, p=0.10). More than 50% of LRRK2-PD with malignancies had ≥ 2 tumors in their lifetime and had at least 1 family member with cancer. The most frequent malingnancies in our LRRK2-PD coohort were cutaneous melanomas, hematological malignancies, uterine and breast cancers. The prevalence of patients with T2-DM was significantly higher in LRRK2-PD (28.57%) patients than in NM-PD (5.88%, p= 0.01) and GBA1-PD (8.33%, p= 0.02).

Conclusion: This study highlighted that LRRK2-PD are likely to be more susceptible to specific malinganceis and to T2-DM compared to GBA1-PD and NM-PD. If confirmed, the management of these patients could be improved by providing not only follow-up for PD, but also early screening of malignancies and T2-DM condition.

This abstract was previously presented at the 10° Società Italiana Parkinson e Disordini del Movimento/LIMPE-DISMOV ETS Congress; Milan, Italy; 10-12 April 2024.

References: [1] V. Yahya, A. Di Fonzo, and E. Monfrini, ‘Genetic Evidence for Endolysosomal Dysfunction in Parkinson’s Disease: A Critical Overview’, Int. J. Mol. Sci., vol. 24, no. 7, p. 6338, Mar. 2023, doi: 10.3390/ijms24076338.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/comorbidities-in-genetic-parkinsons-disease-comparison-between-lrrk2-gba1-and-non-mutated-pd/