The Orphanet Nomenclature of rare diseases: a standard terminology for improved patient recognition and data interoperability

Although individually uncommon, rare diseases (RD) affect an estimated 300 million people worldwide. Establishing a public health approach to RD requires counting diseases and affected patients. However, RD are under-represented in medical terminologies, with only a small fraction of RD possessing specific and unambiguous codes, and those codes not being explicitly designated as rare.

To tackle the challenge of RD codification and interoperability, Orphanet has developed a nomenclature of RD that provides unique and time-stable disease identifiers (ORPHAcodes) and meets the gold standards for implementation in health information systems and systematic research collections. The Orphanet Nomenclature of RD is multilingual and versioned; its development and updates rely on standardized procedures, manual curation and expert validation, reflecting advancements in RD knowledge and clinical practice.

This work provides an overview of the Orphanet Nomenclature and classification system for RD, detailing its production, update and mapping methodology. As of July 2025, the Orphanet Nomenclature contains a total of 6,527 RD, multiclassified into 29 classifications, each corresponding to a medical domain, accurately representing the complex multisystemic nature of RD. Extensive qualified mappings ensure semantic interoperability across multiple terminologies. Overall, 97.4% of RD are mapped to at least one ICD-10 code (with only 6.3% exhibiting an exact equivalence), 71.7% are mapped to at least one ICD-11 code (15.3% with an exact equivalence) and 93.8% are mapped to SNOMED CT (all with an exact equivalence). Genetic diseases represent 72.2% of all RD, and 63.4% are mapped to at least one phenotypic OMIM number.

By addressing the underrepresentation of RD in medical terminologies, ORPHAcodes facilitate accurate patient identification, advance research and healthcare interoperability, and help in shaping public health policies. The recognition of the Orphanet Nomenclature as the most appropriate terminology for RD clinical coding in Europe underscores its critical role in the global RD ecosystem.