Edition of 06 December 2019

A comment published in the Nature Drug Discovery, one of the journals of the Nature publishing group, raised the need of coordinated efforts to more precisely define rare diseases, because a lack of agreement in current rare disease definitions across the multiple resources using diverse terminologies (most of them either Orphanet or OMIM) affect patient resources, diagnosis and treatment approaches, and research on rare disease mechanisms and potential therapies. As patients with rare diseases are estimated to constitute as much as 6% of the population, there is increasing societal pressure to develop diagnostics and therapies for rare diseases. Consequently, there is an urgent need to more precisely define rare diseases and to improve access to accurate information on such diseases in order to realise the goals of precision medicine for the many affected people. However, at present, it seems not even possible to accurately say how many rare diseases there are, when one combines the different databases.

Regulators, scientists, clinicians and patient advocacy groups often cite 7,000 as the number of rare diseases, or between 5,000 and 8,000, depending on the source (see Related links). Why do estimates of the number of rare diseases vary so widely? One reason is the aforementioned lack of consistency in defining discrete disease entities and their incidence in different countries or demographics. Another reason is computational differences and imperfections in the current terminologies. While the consensus process to harmonise disease definitions in the Monarch Disease Ontology by a large number of terminological resources is still ongoing, the estimation of 10,000 rare diseases could be inaccurate. This number was obtained by taking into account of the hierarchical structure of existing disease terminologies, so mixing up different levels of granularity.

Orphanet has adopted a clinical definition for rare diseases, in order to include all rare diseases, genetic or not, and usable for rare disease codification in health systems and registries. In its hierarchical classification, the Orphanet nomenclature of rare diseases (ORPHAcodes) includes the most detailed level as subtypes of diseases, in order to allow for representation of the most up-to-date knowledge, as well as groups of rare diseases, allowing for aggregation of data. An article published concomitantly in the European Journal of Human Genetics establishes though the number of clinically defined rare diseases (excluding subtypes and groups) to be around 6,000, allowing for a worldwide global point prevalence estimation at 3,5 to 6 % of the population. This article underlines the importance of widely acknowledging a clear definition of what a rare disease is in order to take action.

It is clear that all involved actors and partners must join forces globally and across resources, clinically and computationally, to collect, consolidate and curate the most robust and up-to-date knowledge on rare diseases. A call is made for funding and regulatory agencies, patient advocacy groups and all other organisations in the rare diseases field to support a coordinated effort to agree, in a geopolitically neutral manner, what constitutes a discrete rare disease.