A global survey about undiagnosed rare diseases: perspectives, challenges, and solutions

Abstract

Background: Undiagnosed rare diseases (URDs) are a complex and multifaceted challenge, especially in low-and medium-income countries. They affect individuals with unique clinical features and lack a clear diagnostic label. Although the Undiagnosed Diseases Network International (UDNI) definition of URDs is not universally accepted, it is widely recognized.

Methods: We surveyed UDNI members and participants from other countries to explore the challenges posed by URDs and identify possible solutions. Participation in the survey was completely voluntary.

Results: The survey revealed a need for more consensus on a universally accepted definition for URDs. Still, the UDNI definition gained widespread recognition and serves as a valuable framework for understanding and addressing the challenges of URDs. In addition to national or international networks, fostering a more substantial engagement and resource-sharing ethos among member countries is critical. Despite advances in genomics and diagnostic tools, the diagnostic journey for people living with URDs (PLURDs) remains arduous and often inconclusive. The availability of specialized centers and the utilization of whole exome sequencing (WES) and whole genome sequencing (WGS) vary across countries, with disparities due to healthcare systems, economic status, and government policies. Advocacy groups play a crucial role in supporting PLURDs.

Conclusion: A unified commitment to prioritizing URDs on the global health agenda, paired with targeted funding, stipulated national strategies, and aligned international cooperation, is imperative to leveling the playing field for the diagnosis and management of URDs and capitalizing on the potential of Advocacy Groups as allies in this endeavor.

Keywords: advocacy groups; diagnostic journey; genomic diagnosis; healthcare disparities; people living with URDs (PLURDs); undiagnosed rare diseases (URDs).

Figure 1

Distribution of the answer to the question “Which of the following definitions fit with your undiagnosed rare diseases activities?” The possible answers were (A) “activities for people living with rare diseases that do not have a diagnosis yet,” (B) “activities for people living with rare diseases not yet discovered by medical science,” and (C) “activities related to misdiagnosis.” The respondents could give multiple answers. (A) Illustrates the individual responses to the question; (B) considers the possible multiple combinations of responses.

Figure 2

Distribution of the answer to the question “Which of the following options should be included in the definition of ‘undiagnosed rare disease’ in your opinion?” The possible answers were (A) “People with unique characteristics of their disorder who have already been extensively examined, and for which obvious diagnoses have been discarded (UDNI definition),” (B) “A new disease,” and (C) “Rare diseases missed diagnosis;” the respondents could give multiple answers. (A) Illustrates the individual responses to the questions; (B) considers the possible multiple combinations of responses.

Figure 3

(A) Distribution of the answer to the question “Is there a national program/strategy for undiagnosed rare diseases in your country?” (B) Distribution of the answer to the question, “Are there centers dedicated to the care of undiagnosed rare diseases in your country?”

Figure 4

Distribution of the answers to the questions about the availability of Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) within different healthcare systems.