Endothelial dysfunction in Fabry disease: retinal biomarkers link cardiac GLA gene variants with chronic inflammation

npj Genomic Medicine, vol. 11, pp. 6

Abstract

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by variants in the alpha-galactosidase A gene (GLA). Cardiac complications are a major cause of mortality, but the large number of variants complicate early identification of at-risk patients. In this study, we assessed the microcirculation using Retinal Vessel Analysis (RVA) in 63 FD patients age- and gender-matched to 60 healthy controls, analyzing associations between RVA parameters, cardiac involvement, and GLA variants. FD patients showed reduced venular flicker-induced dilation, narrower retinal arterioles, and a lower arteriolar-to-venular ratio. Impaired retinal microcirculation was associated with cardiac involvement, and patients with cardiac-associated GLA variants exhibited narrower retinal arterioles. Markers of inflammation and endothelial dysfunction (ED) were significantly higher in FD patients. Higher inflammatory levels correlated with altered retinal microcirculation in patients carrying cardiac-associated GLA variants. RVA detects microvascular ED in FD patients and may serve as a non-invasive biomarker for cardiovascular risk stratification. Registration: https://clinicaltrials.gov/study/NCT06758648 ; Unique identifier: NCT06758648.

Authors 16

1. Timon Wallraven

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

2. Claudia Regenbogen

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

3. Roman Günthner

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

4. Andrea Ribeiro

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

5. Javier Carbajo-Lozoya

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

6. Nora Hannane

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

7. Michael Wunderle

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

8. Abdelrahman Assaf

   Technical University of Munich · TUM Klinikum

   Affiliation as printed

   TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

9. Maciej Lech

   Ludwig-Maximilians-Universität München · LMU Klinikum

   Affiliation as printed

   Medizinische Klinik und Poliklinik IV, LMU University Hospital Munich, Munich, Germany

10. H Hanssen

    University of Basel

    Affiliation as printed

    Department of Sport, Exercise and Health, Preventive Sports Medicine and Systems Physiology, University of Basel, Basel, Switzerland

11. Lukas Streese

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Nephrology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

12. Derralynn A. Hughes

    University College London · Royal Free London NHS Foundation Trust

    Affiliation as printed

    Lysosomal Storage Disorders Unit, The Royal Free London NHS Foundation Trust, University College London, London, United Kingdom

13. B Haller

    Technical University of Munich · TUM Klinikum

    Affiliation as printed

    TUM School of Medicine and Health, Institute of AI and Informatics in Medicine, TUM University Hospital, Technical University of Munich, Munich, Germany

14. Konstantin E. Kotliar Aachen

    FH Aachen

    Affiliation as printed

    Aachen University of Applied Sciences, Jülich, Germany

15. Uwe Heemann

    Technical University of Munich · TUM Klinikum

    Affiliation as printed

    TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany

16. Christoph Schmaderer corresponding

    Technical University of Munich · TUM Klinikum · German Center for Infection Research

    Affiliation as printed

    German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany. Christoph.Schmaderer@mri.tum.de

    TUM School of Medicine and Health, Department of Nephrology, TUM University Hospital, Technical University of Munich, Munich, Germany. Christoph.Schmaderer@mri.tum.de