Undiagnosed Diseases: Italy-US Collaboration and International Efforts to Tackle Rare and Common Diseases Lacking a Diagnosis

  • Domenica Taruscio
  • Giovanna Floridia
  • Marco Salvatore
  • Stephen C. Groft
  • William A. Gahl
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1031)


Rare diseases (RD), according to European Union criteria, affect 5 per 10,000 persons, or 30 million people, in the EU; in the USA, RD are defined as conditions that affect fewer than 200,000 individuals in the population (320 million). Most known rare disorders are severe and chronic, with many being degenerative and life threatening. There are roughly 5000–8000 rare diseases (European Commission, DG Health and Food Safety, Public Health, Rare Diseases, Policy.http://ec.europa.eu/health/rare_diseases/policy/index_en.htm. Accessed 19 December 2016; NORD-The National Organization for Rare Diseases: https://rarediseases.org/). Patient populations for individual RD are small and scattered; international collaborations are crucial to pool resources fragmented across individual countries for better diagnosis and treatment. Undiagnosed RD (URD) are conditions that elude diagnosis; some patients wait years for a definitive diagnosis. URD may include groups of unnamed disorders with common characteristics, phenotypically well described diseases, diseases with an unknown molecular basis, or those due to unknown, non-genetic factors.

The US NIH Undiagnosed Diseases Program arose in 2008 to provide a diagnosis for individuals who had long sought one without success; in 2013 a nationwide Undiagnosed Diseases Network was established in the United States. In 2015, the Undiagnosed Disease Network International (UDNI) was established and includes US, Australia, Canada, Japan, Italy and other European countries. Other national initiatives have also been undertaken and are in progress all over the world.


Undiagnosed diseases Networks Programs Initiatives Platforms Databases 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Domenica Taruscio
    • 1
  • Giovanna Floridia
    • 1
    • 2
  • Marco Salvatore
    • 1
  • Stephen C. Groft
    • 3
  • William A. Gahl
    • 4
    • 5
  1. 1.Centro Nazionale Malattie RareIstituto Superiore di SanitàRomeItaly
  2. 2.Bioethics UnitIstituto Superiore di SanitàRomeItaly
  3. 3.National Center for Advancing Translational SciencesNational Institutes of HealthBethesdaUSA
  4. 4.Undiagnosed Diseases Program, Common FundNational Institutes of HealthRockvilleUSA
  5. 5.National Human Genome Research Institute, National Institutes of HealthBethesdaUSA

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