Rare disease nomenclature and coding: challenges, systems, and policies in the global context

Rare diseases (RD) collectively affect millions of people worldwide yet remain poorly represented in generic coding terminologies. This lack of representation impedes patient visibility in health systems, in turn engendering downstream consequences such as negatively impacting patient outcomes, clinical research, and RD policy. This review evaluates the intricacies of the common coding systems currently employed to capture RD, and surveys the coding practices and policies in select countries as they pertain to RD. We analyse published literature, mappings between terminologies, and results from recent European projects to assess the applicability of generic and specific coding standards in clinical and registry settings. Globally, RD coding practices are demonstrated to be inconsistent and highly variable, although often rely on generic terminologies (ICD variations and other broad terminologies). Major drivers include heterogeneous national policies and the reliance on legacy standards. Furthermore, our findings reveal that generic classifications, due to their intended use for statistical purposes, provide limited and uneven coverage for RD and lack mechanisms to flag RD patients who have not yet received a diagnosis. In contrast, the Orphanet nomenclature (ORPHAcodes) offers coverage of all RD in the Orphanet knowledge base, a dedicated code for undiagnosed cases, and mappings to major terminologies, thereby improving patient visibility and data interoperability. We propose that the routine use of ORPHAcodes alongside generic classifications, supported by legal frameworks, governance, and implementation support, will enhance RD outcomes and facilitate RD research and policymaking. Coordinated stakeholder collaboration will be essential to realise these benefits to the RD community.