Prevalence of Fabry Disease among Patients with Parkinson's Disease

Alexandra Lackova; Christian Beetz; Sebastian Oppermann; Peter Bauer; Petra Pavelekova; Tatiana Lorincova; Miriam Ostrozovicova; Kristina Kulcsarova; Jana Cobejova; Martin Cobej; Petra Levicka; Simona Liesenerova; Daniela Sendekova; Viktoria Sukovska; Zuzana Gdovinova; Vladimir Han; Mie Rizig; Henry Houlden; Matej Skorvanek

doi:10.1155/2022/1014950

Prevalence of Fabry Disease among Patients with Parkinson's Disease

Parkinsons Dis. 2022 Jan 24:2022:1014950. doi: 10.1155/2022/1014950. eCollection 2022.

Authors

Alexandra Lackova^{1

2}, Christian Beetz³, Sebastian Oppermann³, Peter Bauer³, Petra Pavelekova^{1

2}, Tatiana Lorincova¹, Miriam Ostrozovicova^{1

2}, Kristina Kulcsarova^{1

2}, Jana Cobejova¹, Martin Cobej¹, Petra Levicka¹, Simona Liesenerova¹, Daniela Sendekova¹, Viktoria Sukovska¹, Zuzana Gdovinova^{1

2}, Vladimir Han^{1

2}, Mie Rizig⁴, Henry Houlden⁴, Matej Skorvanek^{1

2}

Affiliations

¹ Department of Neurology, University of Pavol Jozef Šafárik, Košice, Slovakia.
² Department of Neurology, University Hospital of L. Pasteur, Košice, Slovakia.
³ CENTOGENE GmbH, Rostock, Germany.
⁴ University College London, Institute of Neurology, Department of Neuromuscular Disorders, Queen Square, WC1N 3BG London, UK.

Abstract

Background: An increased prevalence of Parkinson's disease (PD) disease has been previously reported in subjects with Fabry disease (FD) carrying alpha-galactosidase (GLA) mutations and their first-line relatives. Moreover, decreased alpha-galactosidase A (AGLA) enzymatic activity has been reported among cases with PD compared to controls.

Objective: The aim of our study was to determine the prevalence of FD among patients with PD.

Methods: We recruited 236 consecutive patients with PD from February 2018 to December 2020. Clinical and sociodemographic data, including the MDS-UPDRS-III scores and HY stage (the Hoehn and Yahr scale), were collected, and in-depth phenotyping was performed in subjects with identified GLA variants. A multistep approach, including standard determination of AGLA activity and LysoGb3 in males, and next-generation based GLA sequencing in all females and males with abnormal AGLA levels was performed in a routine diagnostic setting.

Results: The mean age of our patients was 68.9 ± 8.9 years, 130 were men (55.1%), and the mean disease duration was 7.77 ± 5.35 years. Among 130 men, AGLA levels were low in 20 patients (15%), and subsequent Lyso-Gb3 testing showed values within the reference range for all tested subjects. In 126 subsequently genetically tested patients, four heterozygous p.(Asp313Tyr) GLA variants (3.2%, MAF 0.016) were identified; all were females. None of the 4 GLA variant carriers identified had any clinical manifestation suggestive of FD.

Conclusions: The results of this study suggest a possible relationship between FD and PD in a small proportion of cases. Nevertheless, the GLA variant found in our cohort is classified as a variant of unknown significance. Therefore, its pathogenic causative role in the context of PD needs further elucidation, and these findings should be interpreted with caution.