More than 7,000 rare diseases are recognized worldwide,5 most of them genetic in origin. These conditions vary widely in presentation and progression, but many are severe and complex, placing extraordinary stress on families, communities and economies. Many require round-the-clock care, generate high out-of-pocket expenses and limit participation in education and employment. Children are disproportionately affected. Around 70% of rare diseases manifest in childhood, and many are life-limiting or fatal. As deaths from preventable illnesses decline, rare diseases are emerging as a leading cause of childhood mortality and disability, including in LMICs. For the purposes of this paper, a rare disease is defined as a condition affecting fewer than one in 2,000 people in any World Health Organization (WHO)-defined region (see Figure 3). This aligns with the Operational Description of Rare Diseases developed by Rare Diseases International and global partners,6 although national thresholds vary worldwide.1.1 The human impact of rare diseases What is a rare disease? FIGURE 3 The Operational Description of Rare Diseases defines a rare condition as one affecting ≤1 in 2,000 people in any WHO-defined region, although national thresholds remain in place and differ globally USA Europe Japan China India < 200,000 people (≈ 1 in 1,650)< 1 in 2,000 people < 50,000 people (≈ 1 in 2,500)Based on national rare disease listBased on policy-linked rare disease lists Source: Rare Diseases International; national policy documents Barriers to diagnosis and care Rare diseases are often under-recognized, even among skilled healthcare professionals. A 2021 cross-national survey found that only 19% of medical practitioners felt confident diagnosing rare diseases.7 This helps explain why the average time to diagnosis in Europe is four to five years,8 and often longer elsewhere. Even when a condition is identified, providers often lack the expertise or resources to guide the next steps in management. Without coordinated systems of care, diagnosis can remain a label rather than the beginning of effective treatment and support. Many patients thus cycle through multiple tests and providers, driving up costs for health systems and delaying timely intervention. Approved therapies also remain scarce: around 95% of rare diseases have no treatment authorized by a major regulatory agency. Drug development continues to be focused on a relatively small number of higher-prevalence rare diseases, while thousands of others still lack effective options. Even when treatments exist, many patients are diagnosed too late to benefit from disease- modifying care, remain undiagnosed or face persistent barriers to coverage and access. These barriers often stem from pricing and reimbursement frameworks that are not well suited to assessing rare diseases, where evidence is often limited. More pragmatic approaches to managing uncertainty could help ensure that effective therapies reach patients sooner. Reducing suffering and empowering families Closing these gaps means patients, families and caregivers can live healthier, more productive lives. They can participate more fully in education, work and community life. This not only reduces suffering but also restores productivity, strengthens family stability and eases pressure on health and social systems. Progress in rare diseases such as cystic fibrosis, sickle cell disease and Duchenne muscular dystrophy demonstrates what is possible when investment aligns with science and coordinated care (see Figure 4). These improvements reflect decades of collaboration and data-driven care, showing how targeted innovation can transform lives across generations. Making Rare Diseases Count: How Better Data Can Unlock a Multitrillion-Dollar Opportunity 7

Making Rare Diseases Count 2026