ADTKD genetic diagnostics in Europe
Where do we stand and what is needed ?
Introduction
Due to its non-specific and variable clinical characteristics, ADTKD (autosomal dominant tubulointerstitial kidney disease) [1,2,3] is often misdiagnosed or not diagnosed at all. Experts suspect a high number of unreported cases. This is unsatisfactory, as an ERKNet-based European ADTKD patient registry is to be set up in the next few years.
Aim
We hypothesize a lack of structures to adequately diagnose ADTKD-MUC1. While next generation sequencing (NGS) panels have been established for ADTKD, they are unable to detect pathogenic MUC1 variants due to their specific location in the VNTR region of the genome. Gene defects in the VNTR region can only be diagnosed with great manual effort, e.g. by SNaPshot minisequencing. Alternative methods such as VNtyper are being developed but are not yet widely available [4].
Method
We used Survey Monkey to conduct a digital survey among 34 leading European ADTKD experts. To identify suitable candidates, we used the ERKNet Expert Finder, the European Patient Advocacy Group (ePAG), the mailing list of the ADTKD-Net project and our own patient's society network. The survey contained 10 questions and was carried out from February 2nd till February 29th, 2024. Each expert was asked to answer the questions as a representative of his country.
Results
The results of our survey are shown in Fig. 1. Countries for which we couldn ́t find ADTKD experts are shaded dark gray. Countries that were not included in the survey are shaded light gray. The 18 countries for which ADTKD 34 experts could be identified are shaded in a color other than grey. The 18 countries represent 79% of the European population, based on 2023 population figures excluding Russia [5]. In other words, our survey had the potential to identify the ADTKD-MUC1 diagnostic status for at least 3⁄4 of the European population. However, experts from 5 countries, representing 7% of the European population, did not answer to our request (shaded blue in Fig. 1). Thus, we were finally able to assess the status of the MUC1 gene test in 13 countries representing 72% of the European population, which is still more than 2/3.
Conclusions
European citizens expect national care systems to provide sufficient resources for disease diagnosis.
For ADTKD, a rare kidney disease that cannot be diagnosed by urine, blood or biopsy, the wide availability of genetic testing diagnostics is of utmost importance. Unfortunately, this is not the case for the ADTKD subtype MUC1. Only for every second European patient a corresponding MUC1 gene diagnostic is definitely available in their country.
As the European ADTKD patient association, we call on all stakeholders in the healthcare systems to take appropriate measures to overcome this unsatisfactory situation.
Acknowledgments:
As an ATKD patient organization, we would like to thank our co- authors for their kind support of our work. In addition, we would like to give special credit to all ADTKD experts participating in our survey.