Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations

BackgroundAutonomic symptoms are among the most important factors determining the quality of life in patients with Parkinson’s disease (PD). This study aimed to assess the profile of autonomic dysfunction symptoms in three groups of patients with genetic PD, carrying mutations in GBA, LRRK2, and PRK...

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Main Authors: Bárbara Maldotti Dalla Corte, Nayron Medeiros Soares, Eurípedes Gomes de Carvalho Neto, Carlos Roberto de Mello Rieder
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1657824/full
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author Bárbara Maldotti Dalla Corte
Bárbara Maldotti Dalla Corte
Nayron Medeiros Soares
Eurípedes Gomes de Carvalho Neto
Eurípedes Gomes de Carvalho Neto
Carlos Roberto de Mello Rieder
Carlos Roberto de Mello Rieder
author_facet Bárbara Maldotti Dalla Corte
Bárbara Maldotti Dalla Corte
Nayron Medeiros Soares
Eurípedes Gomes de Carvalho Neto
Eurípedes Gomes de Carvalho Neto
Carlos Roberto de Mello Rieder
Carlos Roberto de Mello Rieder
author_sort Bárbara Maldotti Dalla Corte
collection DOAJ
description BackgroundAutonomic symptoms are among the most important factors determining the quality of life in patients with Parkinson’s disease (PD). This study aimed to assess the profile of autonomic dysfunction symptoms in three groups of patients with genetic PD, carrying mutations in GBA, LRRK2, and PRKN genes, compared with subjects with sporadic PD.MethodsThis case–control observational secondary analysis of prospectively collected data was performed on 742 patients (485 in the sporadic group, 165 in the LRRK2 group, 85 in the GBA group, and nine in the PRKN group). Autonomic symptoms were evaluated using the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT).ResultsThe GBA group exhibited more severe autonomic linsymptoms than the sporadic group, even after controlling for potential confounders such as disease duration and levodopa equivalent daily dose (linear regression B value = −4.668; Total SCOPA-AUT: p = 0.050; LEDD: p = 0.966; Disease Duration: p = 0.498). The LRRK2 group initially showed more autonomic symptoms, but this did not remain significant after adjustment for disease duration (B value = −3.105; p = 0.189). The PRKN group did not differ significantly from the sporadic group. Subgroup analysis highlighted specific issues including constipation, early satiety, and heat intolerance in both the GBA and LRRK2 groups, orthostatic hypotension in the GBA group and urinary incontinence and excessive perspiration in the LRRK2 group. Despite these subjective reports, objective assessment for orthostatic hypotension revealed no significant inter-group differences.ConclusionThese findings that genetic background may influence the severity of autonomic dysfunction in PD. In particular, patients with GBA mutations appear to experience a greater autonomic symptom burden, underscoring the need for personalized clinical monitoring and further research into genotype-specific disease progression. However, inconsistencies between subjective reports and objective autonomic measures emphasize the importance of employing more refined and sensitive assessment tools. Larger and demographically balanced cohorts are required to confirm these results, especially for the underpowered PRKN.
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spelling doaj-art-cb8b7e76fd1e45aab51bb4924c8415ce2025-08-20T03:07:37ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.16578241657824Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutationsBárbara Maldotti Dalla Corte0Bárbara Maldotti Dalla Corte1Nayron Medeiros Soares2Eurípedes Gomes de Carvalho Neto3Eurípedes Gomes de Carvalho Neto4Carlos Roberto de Mello Rieder5Carlos Roberto de Mello Rieder6Medical Sciences Postgraduate Program, Federal University of Rio Grande do Sul, Porto Alegre, BrazilFederal University of Health Sciences of Porto Alegre, Porto Alegre, BrazilMedical Sciences Postgraduate Program, Federal University of Rio Grande do Sul, Porto Alegre, BrazilMedical Sciences Postgraduate Program, Federal University of Rio Grande do Sul, Porto Alegre, BrazilFederal University of Health Sciences of Porto Alegre, Porto Alegre, BrazilMedical Sciences Postgraduate Program, Federal University of Rio Grande do Sul, Porto Alegre, BrazilFederal University of Health Sciences of Porto Alegre, Porto Alegre, BrazilBackgroundAutonomic symptoms are among the most important factors determining the quality of life in patients with Parkinson’s disease (PD). This study aimed to assess the profile of autonomic dysfunction symptoms in three groups of patients with genetic PD, carrying mutations in GBA, LRRK2, and PRKN genes, compared with subjects with sporadic PD.MethodsThis case–control observational secondary analysis of prospectively collected data was performed on 742 patients (485 in the sporadic group, 165 in the LRRK2 group, 85 in the GBA group, and nine in the PRKN group). Autonomic symptoms were evaluated using the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT).ResultsThe GBA group exhibited more severe autonomic linsymptoms than the sporadic group, even after controlling for potential confounders such as disease duration and levodopa equivalent daily dose (linear regression B value = −4.668; Total SCOPA-AUT: p = 0.050; LEDD: p = 0.966; Disease Duration: p = 0.498). The LRRK2 group initially showed more autonomic symptoms, but this did not remain significant after adjustment for disease duration (B value = −3.105; p = 0.189). The PRKN group did not differ significantly from the sporadic group. Subgroup analysis highlighted specific issues including constipation, early satiety, and heat intolerance in both the GBA and LRRK2 groups, orthostatic hypotension in the GBA group and urinary incontinence and excessive perspiration in the LRRK2 group. Despite these subjective reports, objective assessment for orthostatic hypotension revealed no significant inter-group differences.ConclusionThese findings that genetic background may influence the severity of autonomic dysfunction in PD. In particular, patients with GBA mutations appear to experience a greater autonomic symptom burden, underscoring the need for personalized clinical monitoring and further research into genotype-specific disease progression. However, inconsistencies between subjective reports and objective autonomic measures emphasize the importance of employing more refined and sensitive assessment tools. Larger and demographically balanced cohorts are required to confirm these results, especially for the underpowered PRKN.https://www.frontiersin.org/articles/10.3389/fneur.2025.1657824/fulldysautonomiaParkinson’s diseaseSCOPA-AUTgeneticautonomic
spellingShingle Bárbara Maldotti Dalla Corte
Bárbara Maldotti Dalla Corte
Nayron Medeiros Soares
Eurípedes Gomes de Carvalho Neto
Eurípedes Gomes de Carvalho Neto
Carlos Roberto de Mello Rieder
Carlos Roberto de Mello Rieder
Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
Frontiers in Neurology
dysautonomia
Parkinson’s disease
SCOPA-AUT
genetic
autonomic
title Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
title_full Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
title_fullStr Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
title_full_unstemmed Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
title_short Comparative study of autonomic dysfunction between Parkinson’s disease with LRRK2, PRKN, and GBA mutations
title_sort comparative study of autonomic dysfunction between parkinson s disease with lrrk2 prkn and gba mutations
topic dysautonomia
Parkinson’s disease
SCOPA-AUT
genetic
autonomic
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1657824/full
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