Challenges in diagnosis and treatment of rare diseases: Indian perspective

Case reports published in peer-reviewed scientific journals document either rare diseases or atypical presentations of common diseases. However, the term rare diseases’ has a specific connotation. There is no consensus definition of what constitutes ‘rare diseases’; several definitions are in use. Countries define rare diseases differently based on the disease prevalence, population and therapeutic options. The World Health Organization defines rare disease as a disease with a prevalence of ≤10/10,000 population.[1] In the United States of America, rare diseases are defined as diseases that affect <6.4 in 10,000 people; the European Union defines rare diseases as conditions affecting <5/10,000 persons.[1] While the ‘rare diseases’ may be rare individually, when considered together, they affect 5%–7% of the population, which is significant.[2] New rare diseases are regularly reported in the medical literature. However, approximately 350 rare diseases will cover 80% of all rare disease patients.[3] Rare diseases include genetic disorders, rare cancers, infectious diseases, etc., 80% of rare diseases are genetic in origin and commonly affect younger age groups.[4] The medical community will become familiar with the published rare diseases. A rare disease has a low prevalence that affects a few people. Although rare diseases are uncommon, they collectively affect millions of people worldwide. Their impact on patients, families and healthcare systems is profound, economically and psychologically. Still, they are underrepresented in clinical practice, research and policies. I am writing to underscore the importance of rare diseases as a critical area for medical and scientific attention. In a routine diagnostic approach, we think of common causes first while writing the differential diagnosis. In most of the conditions, rare diagnoses are rarely correct. This ‘diagnostic delay’ often results in unnecessary suffering and missed opportunities for timely intervention. Patients with undiagnosed medical conditions will have mental trauma. Rare diseases often leave patients and their families grappling with delayed diagnoses, limited treatment options and insufficient support. In July 2017, the Ministry of Health and Family Welfare (MoHFW), Government of India had formulated a National Policy for Treatment of Rare Diseases (NPTRD).[5] Subsequently, keeping the earlier policy in abeyance, in November 2018, an Expert Committee was constituted by MoHFW to review the NPTRD, 2017.[5] In 2020, the draft policy was put up for online review and in 2021, National Policy For Rare Diseases, 2021 became available.[5] As per the National Rare Disease Policy, India currently has no standard definition of rare diseases and data on prevalence; as there is no complete epidemiological data, there are no figures on the burden of rare diseases. In India, approximately 450 rare diseases have been identified. The most common rare diseases include haemophilia, primary immunodeficiency disorders, auto-immune diseases, autoinflammatory disorders, lysosomal storage disorders, Hirschsprung disease, Gaucher’s disease, cystic fibrosis, certain muscular dystrophies and some infectious diseases.[5] There are several challenges in approaching rare diseases. Because of complex and overlapping symptoms with more common conditions, rare diseases constitute a diagnostic challenge. A multidisciplinary approach is crucial in diagnosis and management. However, diagnostic tools such as special tests or genetic analysis are often limited and not widely available. Further, treatment options are few and expensive, even when available. As the affected patient populations are small, conducting large-scale research studies on rare diseases is difficult. Rare diseases are difficult to diagnose, and sometimes diagnosis is delayed. Many rare diseases remain undiagnosed or misdiagnosed due to limited clinician awareness and sparse epidemiological data. Advanced genomic tools, such as whole-genome sequencing, offer transformative potential in reducing ‘diagnostic odysseys’. However, the accessibility of such tools in resource-limited settings remains a concern. More time is required to diagnose the rare disease for the first time. However, the time needed for diagnosis will be shorter for the next similar case. Rare diseases suffer from a ‘research paradox,’ where their rarity limits the evidence base while robust data are critical for therapeutic advances. Collaborative international registries and real-world data collection could bridge this gap, fostering a global response to rare disease challenges. Raising public awareness makes a difference and gives families new hope. Patients and caretakers will learn about the treatment options and financial support provided by Non-profit Organisations and Government Institutions. So, there is a need for more rare disease Associations to share information and help each other. Some organisations, like the National Organisation for Rare Disorders, are dedicated to advancing care, research and community support for all rare diseases.[6] Genetic counselling is very much needed in rare diseases that are genetic in origin. The medical community should be aware of these rare disorders for early diagnosis and view rare diseases not as isolated cases but as opportunities for scientific discovery with broader implications for medicine. Advancing research in this area could illuminate pathways relevant to more common conditions and fundamentally transform patient care. There is a need to establish a rare disease registry across countries to have their data, which helps to draft policies and strategies to tackle them. Comprehensive policies that support rare disease research expedite regulatory approval of orphan drugs and ensure equitable access to therapies are urgently needed. World Rare Disease Day is observed every year on 28th February. On rare disease days, patient awareness programmes should be conducted to cover a large portion of the population.[7]