Every year since 2008, on the last day of February, color lights turn on to illuminate buildings and landmarks around the world in commemoration of Rare Disease Day. But beyond that last day of February, for about 350 million people around the world, thinking and living with a rare disease is an everyday occurrence. Rare diseases (RDs) are broadly defined as conditions that affect few people in the general population, the most common definition is that of a disorder that affects about or less than 1 person in 2000. Although this is a very low-prevalence definition for any given disease, collectively more than 8,000 rare diseases have been documented in the literature and therefore the number of people living with rare diseases (PLWRD) is not small; but rather, it is equivalent to the third most populous country of the world or about the US population. Beyond the actual patients, RDs also have an important impact on families, as caregiving responsibilities are often adopted by mothers and the need for specialized medical care, equipment, therapies, and education impacts the economics and dynamics of families.
Other relevant facts about rare diseases include that these conditions are often seen primarily in children, with about 70% of them presenting their first symptoms at birth, during infancy or in the pediatric age. Importantly, RDs constitute a major cause of children mortality and morbidity, with many of them causing lifelong or progressive disability. However, for many of them early diagnosis and intervention is not only possible but crucial to reduce or even avoid mortality and disability. Although, generally observed as childhood diseases, many RDs can also present later in pediatric age or during adulthood. Nevertheless, it is in adults that unfortunately we see the greatest lag in reaching a diagnosis, often because their symptoms are dismissed or the diseases misdiagnosed as common diseases.
Approximately 80% of RDs have a strong genetic component and for about 7000 of these diseases the gene associated with the condition has already been identified, meaning that they can be accurately diagnosed using molecular testing technologies. In the last 15 years, the implementation of genomic technologies has revolutionized the study, diagnosis, management, and most recently therapeutic approaches for RDs. Since the first examples of genomic sequencing to identify the molecular causes of genetic diseases (Lupski et al, 2010) and the impact of that information in patient health and outcomes (Bainbridge et al, 2011; Worthey et al. 2011), genomics has become essential to better understand RDs. Over the last 15 years the investigation and discovery of genes associated with RDs and the mechanisms that cause disease have greatly expanded our understanding of human physiology and the myriad of genes involved in important biological processes for normal development and health (Gonzaga-Jauregui, et al. 2012; Genomics of Rare Diseases, 2021).
Unfortunately, the advances in genomic and other molecular technologies are not reaching PLWRDs equally everywhere. Advanced molecular testing technologies are still expensive for patients and researchers in low- and middle-income countries (LMICs), where a great proportion of patients live and the lack of a diagnosis and guided management is more sorely felt. Lack of awareness from primary care physicians about RDs and the importance of obtaining an accurate molecular diagnosis, combined with the high cost, low availability, lack of coverage by public healthcare systems or even private insurance in LMICs has resulted in a very slow adoption of genomic testing and lack of diagnoses for PLWRDs living in these countries. The impact is not only on having a definitive diagnosis for the disease based on genetic information, but more and more examples of advanced therapies developed to address specific molecular defects in RDs are becoming a reality of great success. However, for PLWRDs in LMICs a lack of molecular diagnosis also translates into less possibilities for accessing advanced treatments, approved or in clinical trials, for their disease.
The impact of genomics in human health in the last decade has been so profound that this has been highlighted by the World Health Organization (WHO) Science Council in its first report in 2022 on “Accelerating access to genomics for global health: Promotion, implementation, collaboration, and ethical, legal, and social issues”. The challenges of adopting and implementing genomic technologies for human health in LMICs are particularly recognized in this report, encouraging WHO Member States to adopt and expand the use of genomics through the identification and overcoming of practical issues that impede implementation. While high-income countries are rapidly moving towards national precision medicine initiatives that have RDs as their first line of evidence for the effectiveness of genomics in terms of cost savings, healthcare usage, and patient outcomes, most LMICs are lagging in appreciating the benefit of investment in genomics for precision medicine and population health. Genomics has the potential to reduce the equity gap in global human health, however for this to become a reality, important policy and economical shifts need to occur not only in LMICs, but also in high-income countries to support global implementation to benefit everyone’s health.
In the context of “Universal Health Coverage” as part of the United Nations’ 2030 Sustainable Development Goals, in December 2021, the UN adopted a resolution specifically on “Addressing the Challenges of Persons Living with a Rare Disease and their Families”. More recently in May 2025, the WHO World Health Assembly adopted the resolution on “Rare Diseases: a Global Health Priority for Equity and Inclusion”, which aims at developing a global action plan to improve diagnosis, treatment, care, and support for PLWRD. While these are important milestones towards the recognition of RDs as an important and unattended global health issue, it is still upon Member States to recognize and address the challenges faced by PLWRD in each specific country.
Increasing awareness, discussing about the challenges faced by PLWRD, listening to their everyday experiences, learning about the many RDs that exist and how to recognize them are not activities of only one day or one month a year, but rather a social responsibility towards 350 million people and their families that live with these conditions and their associated challenges every day. Beyond lightning up landmarks and buildings and making speeches about the unfulfilled needs of PLWRD, which often mostly reflect the deficiencies of national healthcare and social care systems, decision makers should take these opportunities to learn, think, and enact policies and solutions for improved access to diagnosis, care, and treatments for PLWRD and beyond. As we move past the month of February, let us continue to reflect and dialogue about rare diseases and what we can do, individually and collectively, to build a more empathetic and inclusive society for everyone everywhere around the world.