What are rare diseases? How are they classified in ICD-10-CM?

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Since Rare Disease Day is February 28, we wanted to explore what qualifies as a rare disease and how rare diseases are classified in ICD-10-CM. Read more to learn about rare diseases, how many people are affected, and the clinical coding systems used to classify rare diseases.

What is a rare disease?

Rare disease experts have different definitions for rare diseases, and there is no consensus on how many rare diseases there are or how many people they affect. According to the Rare Disease Day website, “a disease is rare when it affects fewer than 1 in 2,000 people.” According to the Rare Disease Day steering committee, there are 300 million people worldwide living with a rare disease. The Rare Disease Day website also states that, in the United States, fewer than 200,000 Americans have been diagnosed with a rare disease. Over 6,000 rare diseases have been identified, of which 72% are genetic.  

However, the United States Congress defined rare diseases differently in the Rare Diseases Act of 2002. According to the public law, a rare disease is a disease that affects fewer than 200,000 individuals in the United States. The Genetic and Rare Diseases Information Center estimates that there are approximately 10,000 rare diseases in the U.S. Moreover, different sources focus on various specialized areas, such as cancer, genetic diseases, infectious diseases, or rare diseases with environmental causes.  

While there currently is no globally consistent set of criteria to define rare diseases, there are several domestic and international organizations that work together to provide accurate and reliable information on rare diseases: GARD, NORD, OMIM, Mondo Disease Ontology and Orphanet. Let’s explore some of these organizations briefly.  

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GARD

GARD, the Genetic and Rare Diseases Information Center is run by the National Institutes of Health in the United States. Its mission is to help the rare disease community in the U.S. to access information, get a diagnosis, and find resources.  

NORD

The mission of the National Organization for Rare Disorders is to assist patients who have been diagnosed with a rare disease to get help with access to medication, diagnostics, caregiver support, and other needs. NORD estimates that 25-30 million Americans are living with a rare disease and states that over 7,000 rare diseases have been identified. NORD also considers all pediatric cancers to be rare, and there are more than 500 types of rare cancers.  

OMIM

The Online Mendelian Inheritance in Man is a free online catalog of human genes and genetic disorders that is intended to be used by physicians and other professionals and students in science and medicine. The database was launched in the early 1960s by Dr. Victor A. McKusick as a catalog of traits and disorders that are passed from parents to offspring. The catalog is updated daily and is biocurated at the McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine.  

Mondo Disease Ontology  

The Mondo Disease Ontology unifies multiple worldwide disease resources to harmonize disease definitions. It uses many other ontologies to determine which terms are equivalent across different resources. This iterative approach helps distinguish precisely equivalent diseases from those that are closely related.  

Orphanet

Orphanet is a consortium of 40 countries across the globe that gathers and improves knowledge on rare diseases. Orphanet maintains the rare disease and multilingual nomenclature known as the ORPHAcodes. As the website states, “Each clinical entity is assigned a unique and time-stable ORPHAcode, around which the rest of the data present in the Orphanet database is structured.” Additionally, Orphanet works to meet three main goals:

1. “Improve the visibility of rare diseases in the fields of healthcare and research by maintaining the Orphanet rare disease nomenclature (ORPHAcodes) which provides a common language to understand each other across the RD [rare diseases] field.”
2. “Provide high-quality information on rare diseases and expertise, ensuring equal access to knowledge for all stakeholders,” and
3. “Contribute to generating knowledge on rare diseases thus piecing together the parts of the puzzle to better understand rare diseases.”  

A disease must be described by at least two independent individuals before it can be registered in Orphanet. The ORPHAcode clinical coding system is updated annually in July.  

How are rare diseases classified in ICD-10-CM?

It is important to note that not every rare disease has a unique code within ICD-10-CM. Unfortunately, this could complicate estimates of the number of affected patients.  

Rare disease foundations and groups can advocate for a unique ICD-10-CM code for a certain rare disease at the biannual ICD-10 Coordination and Maintenance Committee meetings run by the CDC and CMS. For example, the Kabuki Syndrome Foundation led a campaign to secure a unique ICD-10-CM code for this rare epigenetic condition that is characterized by distinctive facial features, growth delays, intellectual disability, and skeletal abnormalities. After a two-year campaign, Kabuki Syndrome was officially recognized with its own ICD-10-CM code that went into effect on October1, 2025: Q89.81. Up until this new code went into effect, Kabuki syndrome fell under the catch-all code Q89.8: Other specified congenital malformations.  

There are other rare diseases that have a unique ORPHAcode but do not have a unique ICD-10-CM code. Some examples of these rare diseases include: acromelanosis, a rare pigmentation anomaly of the skin mostly seen in newborns and young children; and ringed hair disease, an abnormality of the hair shaft.  

There are many benefits for a rare disease to have a unique classification within ICD-10-CM. With a specific code, the following goals can be achieved:

• Insight into the actual number and demographics of patients
• Better understanding of the range and severity of a rare disease’s symptoms
• More insight into the range and effectiveness of treatments, tests, and services
• Streamlined insurance approval process

The Every Life Foundation for Rare Diseases provides a resource guide that explains how diagnosis codes are assigned, updated, and revised. The guide describes the process by which one can propose changes to existing codes or introduce new codes.  

What about rare disease codes in ICD-11?  

While revising ICD for the 11th version, the World Health Organization established a Topic Advisory Group for rare diseases that is managed by Orphanet. ICD-11, which came into effect on January 1, 2022, includes nearly 5,500 rare disease classifications in the ICD-11 code set.  

Conclusion  

Rare diseases are both difficult to diagnose and treat. They are commonly misdiagnosed since there is a wide diversity of rare disorders that have relatively common symptoms. However, there are many organizations that champion rare disease research, so patients and caregivers alike can get the optimal medical care and resources they need.  

Resources

Rare Disease Day. (n.d.). Rare Disease Day. Retrieved December 15, 2025, from https://www.rarediseaseday.org/

Orphanet: an online rare disease and orphan drug data base. Copyright, INSERM 1999. Available on https://www.orpha.net. Accessed (December 17, 2025).

Orphacode. (n.d.). Orphacode. Retrieved December 15, 2025, from https://www.orphacode.org/

RD-Code. (2022, January). Standard procedure and guide for coding with Orphacodes (Final). Retrieved December 15, 2025, from https://www.rd-code.eu/wp-content/uploads/2022/01/826607_D5-4_Standard-procedure-and-guide-for-coding-with-Orphacodes_final.pdf

Orphacode Classifications. (n.d.). Classifications. Retrieved December 15, 2025, from https://classifications.orphacode.org/

Orphacode Mappings. (n.d.). Mappings. Retrieved December 15, 2025, from https://mappings.orphacode.org/

Monarch Initiative. (n.d.). Rare disease. Retrieved December 15, 2025, from https://mondo.monarchinitiative.org/pages/rare-disease/

National Center for Advancing Translational Sciences. (n.d.). About rare diseases. Retrieved December 15, 2025, from https://rarediseases.info.nih.gov/about

Austin, C. P., Cutillo, C. M., Lau, L. P. L., Jonker, A. H., Rath, A., Julkowska, D., ... & Lochmüller, H. (2021). Future of rare diseases research 2017–2027: An IRDiRC perspective. Nature Reviews Drug Discovery, 20(9), 629–639. https://pmc.ncbi.nlm.nih.gov/articles/PMC7771654/

National Organization for Rare Disorders. (n.d.). Rare Diseases. Retrieved December 15, 2025, from https://rarediseases.org/

Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), {date}. World Wide Web URL: https://omim.org/

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