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How many rare diseases are there?

12 January 2023   |  
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Author: Mariavi Ruiz, Senior Scientist at Healx

Mariavi is a senior scientist in our Curation and Disease Selection teams, where she contributes her knowledge of disease biology and preclinical research to the identification of rare disease candidates to continue building our pipeline of new and effective therapies for rare disease patients.

Several factors contribute to the difficulty of identifying and counting rare diseases with accuracy.

On one hand, the definition of what constitutes a rare disease differs between different countries around the world, ranging from 5 to 76 affected individuals per 100,000 people in the general population 1. In Europe, a disease is considered rare when less than 50 / 100 000 individuals are affected, while in the US a rare disease is one affecting less than 200,000 people in the country. On the other hand, their rarity itself can make some conditions pass unnoticed to the international scientific community unless the patients’ symptoms or phenotypes are properly classified and described in the medical literature, and, ideally, the disease aetiology studied and defined. The lower the number of patients affected, the less probable that the disease will be described, classified and studied. Since most clinicians are not experienced in recognising and managing the vast majority of rare diseases, in many cases a rare disease might not be diagnosed for years, or might be misdiagnosed as another more prevalent disease that it might resemble. Finally, computational differences motivated by the use of different nomenclatures or inclusion criteria also have an impact on the estimation of the number of rare diseases 2.

When interrogating the scientific literature, as well as public web pages from official governmental institutions or charities, figures between 5,000 and 8,000 rare diseases are frequently cited, with 7,000 rare diseases being one of the most repeated 3,4. These numbers have remained unchanged over the last 10-15 years, despite hundreds of new disorders being added to databases such as OMIM each year 2, and advances in the identification of new rare medical conditions and their associated causative genes over the last decade thanks to the reduced price and increased availability of techniques such as next-generation sequencing 4,5.

Two recent studies, however, have identified 10,000+ rare diseases by computing and harmonising rare disease information from multiple data sources such as Orphanet, OMIM, GARD, DOID and NCI Thesaurus. The first study was published in 2020 by a group of scientists part of the Monarch Disease Ontology (Mondo) initiative. This study identified 10,393 rare diseases 2. The second study was published in June 2022 as a report performed by the non-profit organisation RARE-X, and it identified 10,867 rare conditions 6. Thus, it is safe to conclude that there are more than 10,000 rare diseases, and this number is likely to increase in the following years as a consequence of increased awareness and improved diagnosis.

How many rare disease patients are there?

Several analyses have tried to estimate the global number of rare disease patients worldwide. Epidemiological studies are limited, for reasons similar to those mentioned above for the estimation of the number of existing rare diseases. It is often quoted that rare diseases affect 6 to 8% of the population. These figures were first referred to in 1992 by three studies that became the basis of the EU legislation on Orphan Products in 1999 7. Some additional estimations were published afterwards, based on limited diseases and population coverage 8-10, or not considering only unique clinical disorders 11, which can lead to double counts by inclusion of groups and subtypes.

The most recent and methodologically solid estimate of the global burden of rare diseases was published in 2020 by a group of Orphanet researchers. After excluding rare cancers, infectious diseases and poisonings, this study estimated that 262.9 to 446.2 million people worldwide are affected by a rare disease, with 17.8 to 30.3 million people in the European Union 1. Considering methodological limitations and the fact that this estimation was based on the World’s population in 2017, a figure of 400 million affected patients worldwide is recommended.

How many rare diseases have a treatment?

When consulting scientific publications, official governmental sources and dissemination and patient webpages, it is commonly affirmed that only around 5-10% of rare diseases have at least one approved treatment. Unfortunately, these figures are usually cited without references, for example in 12-14, making it difficult to determine the underlying source.

Since a study estimating the number of rare diseases with available treatment could not be found, we proceeded to estimate this number based on available data. According to a NORD report from 2020, as of January 1, 2020, 564 orphan products had been approved by the US Food and Drug Administration (FDA) to treat 838 rare diseases. By applying a simple proportion, 7.7 – 8 % rare diseases have an approved drug treatment (based on the RARE-X and Mondo figures cited above, of 10,867 and 10,393 rare diseases, respectively). Even if we are conservative on the number of diseases and restrict to mainly clinical entities, such as Orphanet describes (around 9,300 rare clinical entities), the figure is still similar, at 9%. Please take into consideration that this estimation has not taken into account that some rare conditions can be treated with interventions other than drugs, such as surgery or diet, and that the estimated figure is likely to slowly change year by year as new treatments get approved. Thus, the real number of rare diseases with a treatment is likely to be slightly higher, but it is safe to say that at least 90% of rare diseases do not have a treatment.


  1. Nguengang Wakap, S. et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur. J. Hum. Genet. 28, 165–173 (2020).
  2. Haendel, M. et al. How many rare diseases are there? Nat. Rev. Drug Discov. 19, 77–78 (2020)
  3. Griggs, R. C. et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol. Genet. Metab. 96, 20–26 (2009)
  4. Seaby, E. G. & Ennis, S. Challenges in the diagnosis and discovery of rare genetic disorders using contemporary sequencing technologies. Brief. Funct. Genomics 19, 243–258 (2020)
  5. Marwaha, S., Knowles, J. W. & Ashley, E. A. A guide for the diagnosis of rare and undiagnosed disease: beyond the exome. Genome Med. 14, 23 (2022)
  6. , K., Lefebvre, S., Levine, D. S., Erler, W. & Hume, T. The Power of Being Counted. https://rare-x.org/case-studies/the-power-of-being-counted/ (2022)
  7. European Union. Regulation (EC) N°141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products. (2000)
  8. Mazzucato, M., Visonà Dalla Pozza, L., Manea, S., Minichiello, C. & Facchin, P. A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry. Orphanet J. Rare Dis. 9, 37 (2014)
  9. Walker, C. E. et al. The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. Genet. Med. Off. J. Am. Coll. Med. Genet. 19, 546–552 (2017)
  10. Chiu, A. T. G., Chung, C. C. Y., Wong, W. H. S., Lee, S. L. & Chung, B. H. Y. Healthcare burden of rare diseases in Hong Kong – adopting ORPHAcodes in ICD-10 based healthcare administrative datasets. Orphanet J. Rare Dis. 13, 147 (2018)
  11. Ferreira, C. R. The burden of rare diseases. Am. J. Med. Genet. A. 179, 885–892 (2019)
  12. Willmer, G. The building blocks to make rare disease treatments more common. Horizon, the EU Research and Innovation Magazine (2022)
  13. The Lancet Diabetes Endocrinology, Editorial. Spotlight on rare diseases. Lancet Diabetes Endocrinol. 7, 75 (2019)
  14. Kaufmann, P., Pariser, A. R. & Austin, C. From scientific discovery to treatments for rare diseases – the view from the National Center for Advancing Translational Sciences – Office of Rare Diseases Research. Orphanet J. Rare Dis. 13, 196 (2018).

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