Fabry disease is a lysosomal storage disorder resulting from impaired alpha-galactosidase A (α-Gal A) enzyme activity due to mutations in the GLA gene. Currently, powerful diagnostic tools and in vivo research models to study Fabry disease are missing, which is a major obstacle for further improvements in diagnosis and therapy. Here, we explore the utility of urine-derived primary cells of Fabry disease patients. Viable cells were isolated and cultured from fresh urine void. The obtained cell culture, modeling the renal epithelium, is characterized by patient-specific information. We demonstrate that this non-invasive source of patient cells provides an adequate cellular in vivo model as cells exhibit decreased α-Gal A enzyme activity and concomitant globotriaosylceramide accumulation. Subsequent quantitative proteomic analyses revealed dysregulation of endosomal and lysosomal proteins indicating an involvement of the Coordinated Lysosomal Expression and Regulation (CLEAR) network in the disease pathology. This proteomic pattern resembled data from our previously described human podocyte model of Fabry disease. Taken together, the employment of urine-derived primary cells of Fabry disease patients might have diagnostic and prognostic implications in the future. Our findings pave the way towards a more detailed understanding of pathophysiological mechanisms and may allow the development of future tailored therapeutic strategies.

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Background Frequent outbreaks around the globe and endemic appearance in different parts of the world emphasize the substantial risk of hantavirus diseases. Increasing incidence rates, trends of changing distribution of hantaviruses species and new insights into clinical courses of hantavirus diseases call for multinational surveillance. Furthermore, evidence-based guidelines for the management of hantavirus diseases and scoring systems, which allow to stratify patients into risk categories, are lacking. Methods/Study design HantaReg is a novel registry platform facilitating multinational research of hantavirus-caused diseases, such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HantaReg provides an electronic case report form and uses the General Data Protection Regulation compliant platform clinicalsurveys.net, which can be accessed from any internet browser in the world. Having a modular structure the registry platform is designed to display or hide questions and items according to the documented case (e.g. patient with HFRS vs. HCPS) to facilitate fast, but standardized data entry. Information categories documented into HantaReg are demographics, pre-existing diseases, clinical presentation, diagnostic and therapeutic approaches, as well as outcome. Conclusion HantaReg is a novel, ready to use platform for clinical and epidemiological studies on hantavirus diseases and facilitates the documentation of the disease course associated with hantavirus infections. HantaReg is expected to promote international collaboration and contributes to improving patient care by the analysis of diagnostic and treatment pathways for hantavirus diseases and will provide evidence for robust treatment recommendations. Moreover, HantaReg enables the development of prognosis-indicating scoring systems for patients with hantavirus disease.