rare disease

There is no single, widely accepted definition for rare diseases. Some definitions rely solely on the number of people living with a disease, and other definitions include other factors, such as the existence of adequate treatments or the severity of the disease.

In the United States, the Rare Diseases Act of 2002 defines rare disease strictly according to prevalence, specifically "any disease or condition that affects fewer than 200,000 people in the United States",{{cite web| url=http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=107_cong_public_laws&docid=f:publ280.107 | title=Rare Disease Act of 2002| publisher =United States Congress| access-date=21 January 2022}} or about 1 in 1,500 people. This definition is essentially the same as that of the Orphan Drug Act of 1983, a federal law that was written to encourage research into rare diseases and possible cures.

In Japan, the legal definition of a rare disease is one that affects fewer than 50,000 patients in Japan, or about 1 in 2,500 people.{{cite web | url=http://malattierare.regione.veneto.it/inglese/dicosaparliamo_ing.php | title=Rare diseases: what are we talking about?| publisher=Rare diseases centre – Venetian Region – Italy| access-date=21 January 2022}}

The European Commission on Public Health defines rare diseases as "life-threatening or chronically debilitating diseases which are of such low prevalence that special combined efforts are needed to address them".{{cite web | access-date=19 May 2009 | title=Useful Information on Rare Diseases from an EU Perspective | url=http://ec.europa.eu/health/ph_information/documents/ev20040705_rd05_en.pdf | publisher=European Commission}} The term low prevalence is later defined as generally meaning fewer than 1 in 2,000 people.{{cite journal | vauthors = Baldovino S, Moliner AM, Taruscio D, Daina E, Roccatello D | title = Rare Diseases in Europe: from a Wide to a Local Perspective | journal = The Israel Medical Association Journal | volume = 18 | issue = 6 | pages = 359–63 | date = June 2016 | pmid = 27468531 | url = http://www.ima.org.il/FilesUpload/IMAJ/0/200/100025.pdf | type = Review }} Diseases that are statistically rare, but not also life-threatening, chronically debilitating, or inadequately treated, are excluded from their definition.

The definitions used in the medical literature and by national health plans are similarly divided, with definitions ranging from 1/1,000 to 1/200,000.

Because of definitions that include reference to treatment availability, a lack of resources, and severity of the disease, the term orphan disease is frequently used as a synonym for rare disease. But in the United States and the European Union, "orphan diseases" have a distinct legal meaning.

The United States' Orphan Drug Act includes both rare diseases and any non-rare diseases "for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will [be] recovered from sales in the United States of such drug" as orphan diseases.[https://web.archive.org/web/20090605073341/http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/Overview/ucm119477.htm Orphan Drug Act] §526(a)(2)

The European Organization for Rare Diseases (EURORDIS) also includes both rare diseases and neglected diseases into a larger category of "orphan diseases".{{cite web | url= http://www.eurordis.org/IMG/pdf/princeps_document-EN.pdf | title=Rare Diseases: Understanding This Public Health Priority | publisher= European Organisation for Rare Diseases (EURORDIS) | date= November 2005 | access-date=16 May 2009}}

Prevalence (number of people living with a disease at a given moment), rather than incidence (number of new diagnoses in a given year), is used to describe the impact of rare diseases. The Global Genes Project estimates some 300 million people worldwide are affected by a rare disease.

The European Organization for Rare Diseases (EURORDIS) estimates that between 3.5 and 5.9% of the world's population is affected by one of approx. 6,000 distinct rare diseases identified to-date.{{Cite web |title=What is a rare disease? |url=https://www.eurordis.org/information-support/what-is-a-rare-disease/ |access-date=2022-08-04 |website=eurordis.org |language=en-US}} European Union has suggested that between 6 and 8% of the European population could be affected by a rare disease sometime in their lives.{{Cite journal |last1=Nguengang Wakap |first1=Stéphanie |last2=Lambert |first2=Deborah M. |last3=Olry |first3=Annie |last4=Rodwell |first4=Charlotte |last5=Gueydan |first5=Charlotte |last6=Lanneau |first6=Valérie |last7=Murphy |first7=Daniel |last8=Le Cam |first8=Yann |last9=Rath |first9=Ana |date=2020 |title=Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database |journal=European Journal of Human Genetics |language=en |volume=28 |issue=2 |pages=165–173 |doi=10.1038/s41431-019-0508-0 |pmid=31527858 |pmc=6974615 |issn=1476-5438}}

About 80% of rare diseases have a genetic component and only about 400 have therapies, according to Rare Genomics Institute.{{Cite book|title=Rare Diseases, Diagnosis, Therapies, and Hope|last1=Sanfilippo|first1=Ana|last2=Lin|first2=Jimmy|publisher=Rare Genomics Institute|year=2014|location=St. Louis, MO|pages=6}}

Rare diseases can vary in prevalence between populations, so a disease that is rare in some populations may be common in others. This is especially true of genetic diseases and infectious diseases. An example is cystic fibrosis, a genetic disease: it is rare in most parts of Asia but relatively common in Europe and in populations of European descent. In smaller communities, the founder effect can result in a disease that is very rare worldwide being prevalent within the smaller community. Many infectious diseases are prevalent in a given geographic area but rare everywhere else. Other diseases, such as many rare forms of cancer, have no apparent pattern of distribution but are simply rare. The classification of other conditions depends in part on the population being studied: All forms of cancer in children are generally considered rare,{{cite web |url=http://www.ecpc-online.org/newsletter/member-updates/168-rare-cancer-day.html |title=02/2009: Rare Cancers on Rare Disease Day |publisher=Ecpc-online.org |date=2009-02-28 |access-date=2012-09-24 |url-status=dead |archive-url=https://web.archive.org/web/20110726131436/http://www.ecpc-online.org/newsletter/member-updates/168-rare-cancer-day.html |archive-date=26 July 2011 }} because so few children develop cancer, but the same cancer in adults may be more common.

Estimating the incidence and prevalence of rare diseases is a complex process due to their wide range of prevalence rates. Rare diseases with higher prevalences can be estimated through a screening panel or patient registries, while diseases which are exceedingly rare may only be able to be estimated through a multi-step nationwide reporting process or case reports. Therefore, the data is often incomplete and complex to amalgamate, compare, and update continually. The Genetic and Rare Diseases Information Center at the National Center for Advancing Translational Sciences curates and compiles rare disease prevalence and incidence from PubMed articles and abstracts using a combination of deep learning algorithms and rare disease experts.{{Cite journal |last1=Kariampuzha |first1=William |last2=Alyea |first2=Gioconda |last3=Qu |first3=Sue |last4=Sanjak |first4= Jaleal |last5=Mathé |first5=Ewy |last6=Sid |first6=Eric |last7= Chatelaine |first7=Haley |last8=Yadaw |first8=Arjun |last9=Xu |first9=Yanji |last10=Zhu |first10=Qian |date=2023 |title=Precision information extraction for rare disease epidemiology at scale |journal=Journal of Translational Medicine |language=en |volume=21 |issue=1 |page=157 |doi=10.1186/s12967-023-04011-y |pmid=36855134 |pmc=9972634 |doi-access=free }}

About 40 rare diseases have a far higher prevalence in Finland; these are known collectively as Finnish heritage disease. Similarly, there are rare genetic diseases among the Amish religious communities in the US and among ethnically Jewish people.

A rare disease is defined as one that affects fewer than 200,000 people across a broad range of possible disorders.{{cite web |title=Genetic and Rare Diseases Information Center |url=https://rarediseases.info.nih.gov/diseases |publisher=National Center for Advancing Translational Sciences, US National Institutes of Health |access-date=12 October 2019 |date=2019}} Chronic genetic diseases are commonly classified as rare.{{cite journal | vauthors = Aymé S, Schmidtke J | title = Networking for rare diseases: a necessity for Europe | journal = Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | volume = 50 | issue = 12 | pages = 1477–83 | date = December 2007 | pmid = 18026888 | doi = 10.1007/s00103-007-0381-9 | s2cid = 36072660 }} Among numerous possibilities, rare diseases may result from bacterial or viral infections, allergies, chromosome disorders, degenerative and proliferative causes, affecting any body organ. Rare diseases may be chronic or incurable, although many short-term medical conditions are also rare diseases.

The NIH's Office of Rare Diseases Research (ORDR) was established by H.R. 4013/Public Law 107–280 in 2002.{{Cite web|url=https://georgewbush-whitehouse.archives.gov/news/releases/2002/11/20021106-3.html|title=President Signs Bills into Law|website=georgewbush-whitehouse.archives.gov}} H.R. 4014, signed the same day, refers to the "Rare Diseases Orphan Product Development Act".{{cite web |url=http://www.rarediseases.org/washington/bush_signs |title=NORD – National Organization for Rare Disorders, Inc. |url-status=dead |archive-url=https://web.archive.org/web/20080618210143/http://www.rarediseases.org/washington/bush_signs |archive-date=18 June 2008 }} Similar initiatives have been proposed in Europe.{{Cite web|url=https://international.orphanews.org/newsletter-en/id-080319.html|title=Newsletter|website=OrphaNews – International}} The ORDR also runs the Rare Diseases Clinical Research Network (RDCRN). The RDCRN provides support for clinical studies and facilitating collaboration, study enrollment and data sharing.{{Cite web|url=https://www.rarediseasesnetwork.org/about|title=About Us|first=Rare Diseases Clinical Research|last=Network|website=Rare Diseases Clinical Research Network}}

In 2013, the United Kingdom government published The UK Strategy for Rare Diseases which "aims to ensure no one gets left behind just because they have a rare disease", with 51 recommendations for care and treatment across the UK to be implemented by 2020.{{cite book|title=The UK Strategy for Rare Diseases|date=2013|publisher=Department of Health|url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/260562/UK_Strategy_for_Rare_Diseases.pdf|access-date=26 October 2017}} Health services in the four constituent countries agreed to adopt implementation plans by 2014, but by October 2016, the Health Service in England had not produced a plan and the all-party parliamentary group on Rare, Genetic and Undiagnosed Conditions produced a report Leaving No One Behind: Why England needs an implementation plan for the UK Strategy for Rare Diseases in February 2017.{{cite book|last1=All Party Parliamentary Group on Rare, Genetic and Undiagnosed Conditions|title=Leaving No One Behind: Why England needs an implementation plan for the UK Strategy for Rare Diseases|date=February 2017|publisher=Rare Disease UK|url=http://www.raredisease.org.uk/media/2783/appg-report-on-the-implementation-of-the-uk-strategy-for-rare-diseases-in-england.pdf|access-date=29 January 2018}} In March 2017 it was announced that NHS England would develop an implementation plan.{{cite web|title=The Westminster All Party Parliamentary Group on Rare, Genetic and Undiagnosed Conditions|url=https://www.geneticalliance.org.uk/appg/|publisher=Genetic Alliance UK|access-date=26 October 2017}} In January 2018 NHS England published its Implementation Plan for the UK Strategy for Rare Diseases.{{cite book|title=Implementation Plan for the UK Strategy for Rare Diseases|date=29 January 2018|publisher=NHS England|url=https://www.england.nhs.uk/wp-content/uploads/2018/01/implementation-plan-uk-strategy-for-rare-diseases.pdf|access-date=29 January 2018}} In January 2021 the Department of Health and Social Care published the UK Rare Diseases Framework, a policy paper which included a commitment that the four nations would develop action plans, working with the rare disease community, and that "where possible, each nation will aim to publish the action plans in 2021".{{cite web |title=The UK Rare Diseases Framework |url=https://www.gov.uk/government/publications/uk-rare-diseases-framework/the-uk-rare-diseases-framework |website=GOV.UK |publisher=Department of Health and Social Care |access-date=12 January 2021 |language=en |date=9 January 2021}} NHS England published England Rare Diseases Action Plan 2022 in February 2022.{{cite web |title=England Rare Diseases Action Plan 2022 |url=https://www.gov.uk/government/publications/england-rare-diseases-action-plan-2022/england-rare-diseases-action-plan-2022 |website=GOV.UK |publisher=Department of Health & Social Care |access-date=22 March 2022 |language=en}}

Organisations around the world are exploring ways of involving people affected by rare diseases in helping shape future research, including using online methods to explore the perspectives of multiple stakeholders.{{cite journal | vauthors = Nunn JS, Gwynne K, Gray S, Lacaze P | title = Involving people affected by a rare condition in shaping future genomic research | journal = Research Involvement and Engagement | volume = 7 | issue = 1 | pages = 14 | date = March 2021 | pmid = 33722276 | pmc = 7958104 | doi = 10.1186/s40900-021-00256-3 | doi-access = free }}

Rare Disease Day is held in Europe, Canada, the United States, and India on the last day of February (thus, in leap years, on February 29, the rarest day){{cite web |title=Rare Disease Day |url=https://geneticalliance.org.uk/campaigns-and-research/rare-disease-day/ |website=Genetic Alliance |access-date=29 February 2024 |language=en |quote=chosen because 29 February is the rarest day of the year}} to raise awareness for rare diseases.{{cite news | title=February 29th Is The First Rare Disease Day | url=http://www.medicalnewstoday.com/articles/98767.php | date=28 February 2008 | access-date=14 February 2009 | work=Medical News Today | archive-date=7 June 2020 | archive-url=https://web.archive.org/web/20200607195811/https://www.medicalnewstoday.com/articles/98767 | url-status=dead }}{{cite web | url=http://www.rarediseases.org/rare_disease_day/rare_disease_day_info | title=Join Us In Observing Rare Disease Day On Feb. 28, 2009! | publisher=National Organization for Rare Disorders | url-status=dead | archive-url=https://web.archive.org/web/20081218211426/http://www.rarediseases.org/rare_disease_day/rare_disease_day_info | archive-date=18 December 2008 }}{{cite web | url=http://savemylife.in/blog/building-a-strong-rare-disease-community-how-you-can-help/ | title=Building a Strong Rare Disease Community: How You Can Help | access-date=5 March 2025 | date=5 March 2025 }}{{cite web|date=2021-02-28|title=Rare Diseases Day: Experts call for more research for patients' welfare|url=https://indianexpress.com/article/lifestyle/health/rare-diseases-day-experts-call-for-more-research-for-patients-welfare-7208733/|access-date=2021-09-12|website=The Indian Express|language=en}} There are a number of non-profit and charitable organisations which push for further awareness, interest, and engagement in the subject of rare diseases, including EURORDIS, Genetic Alliance UK, and the Rare Revolution Magazine.{{cite web |title=Rare Revolution Magazine |url=https://rarerevolutionmagazine.com/ |website=rarerevolutionmagazine.com/ |access-date=27 September 2023}}

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• National Organization for Rare Disorders (NORD)
• Undiagnosed Diseases Network (UDN)
• Orphanet (Online portal for rare diseases and orphan drugs)
• ICD coding for rare diseases
• List of rare disease organisations
• Orphanet Journal of Rare Diseases (academic journal)
• Rare Disease Day
• Idiopathic disease
• Mystery Diagnosis
• Health care rationing
• Ultra-rare disease

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{{Reflist}}

• [https://www.who.int/standards/classifications/frequently-asked-questions/rare-diseases ICD-11 FAQ]
• [https://rarediseases.info.nih.gov/about-gard/pages/23/about-gard Database of rare diseases] at GARD, The United States Genetic and Rare Diseases Information Center
• [http://www.orpha.net Database of rare diseases] at Orphanet
• [https://rarediseases.org/ National Organization for Rare Disorders] (United States)
• [https://www.raredisease.org.uk/ Rare Disease UK]
• [https://www.mendelian.co/ Rare diseases search engine]
• [https://rarerevolutionmagazine.com/ Rare Revolution Magazine]

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