It is estimated that there are approximately 7,000–8,000 rare diseases worldwide. While each rare disease affects a smaller population individually, according to an estimate collectively they impact 3.5–5.9% of the global population amounting to approximately 400 million people globally. (1, 2) According to the World Health Organization (WHO), rare diseases are debilitating, lifelong disorders whose prevalence is less than one per 1,000 persons. However, there is no single, universally accepted prevalence-based definition for rare diseases. Many countries have defined rare diseases in the context of their population, healthcare systems, and resources. (3) In the United States, rare diseases are defined as any condition or disease affecting fewer than 200,000 individuals. In the European Union, rare diseases have been determined to be of low prevalence (fewer than 5 individuals per 10,000). (1) Like many other developing countries, currently India does not have a standard definition for rare diseases. (3) Estimating the exact prevalence of rare diseases in India is challenging due to lack of a comprehensive database, inter-regional disparities, uneven distribution of rare diseases, lack of awareness, and poor access to diagnostic facilities as depicted in Fig. 1. (2, 4)

Rare diseases have emerged as a global public health concern as they can present any time throughout the life span of an individual. More than 80% of these are genetic in origin, with only around 5% having definitive therapies (5). The key characteristic of rare diseases lies in their notable clinical heterogeneity. Individual rare diseases can manifest with a wide range of symptoms, affecting multiple organ systems. The heterogeneity extends beyond symptoms, encompassing a wide range of underlying genetic mutations, metabolic, and infectious etiologies. (6) It is challenging to understand their natural history and pathophysiology, leading to inadequate clinical expertise and diagnostic skills among clinicians. Due to this lack of awareness and appropriate training amongst healthcare professionals and limited accessibility to specialized diagnostic facilities, several hurdles exist in the management of rare diseases. (7, 8) Research on developing new and affordable diagnostic therapies for rare diseases needs to be intensified for ensuring drug accessibility. (9) India's rare disease research landscape is developing slowly. The Government of India launched the National Policy for Treatment of Rare Diseases (NPTRD) in 2017 which expressively mentioned the challenges in formulating a policy without an evidence base. NPTRD was revised and the National Policy for Rare Diseases (NPRD) was formulated in March 2021, with a vision to promote research and development for the diagnosis and treatment of rare diseases. (10) There is a felt need to generate an India-specific database of rare disease patients that could help fill up the knowledge gap, and assist researchers, healthcare providers and policy makers in developing a better understanding of various aspects of rare diseases within the Indian population. It would also facilitate learning for drug regulators, clinicians, communities, organizations, patients and families. (11)

A patient data registry is a valuable tool that collects data on pre-defined variables of patients in a centralized and systematic manner, contributing effectively towards understanding the presentation and course of the disease. (12) Setting up a rare disease registry is a complex process that requires time, effort, specialized knowledge, and consistency. Several aspects need to be taken care of while setting up the registry, like, the design and development of registry, data quality and assurance, inclusion criteria, and ensuring follow-up. (13) There can be various contexts for each country.

The ICMR initiated the “National Registry for Rare and Other Inherited Disorders (NRROID)” in 2019 with an aim to collect systematic, comprehensive, and high-quality data on rare diseases in India and improve the understanding, of demography, clinical features, diagnosis and management of rare diseases with a unique Indian perspective. The larger goal was to develop a database for aiding policy decisions.

This article aims to provide an overview of our experience in designing, developing, and implementing the NRROID, the challenges faced in the due course, and the steps taken to overcome those challenges. We believe that this information would be helpful for clinicians, researchers and policymakers in understanding the process and complexities of setting up a productive rare disease registry.

The registry was initiated by bringing the interested experts in the field together and setting up a charter for the registry. An open call for expressions of interest (EOI) was released by ICMR inviting clinicians and researchers working on rare diseases to become a part of the creation and development of the national rare disease registry. An expert committee screened the EOIs based on the site-selection criteria mentioned below.

Site-selection Criteria:

After site selection, steering groups were constituted by ICMR including participants from selected sites and experts from various specialties, e.g., Pediatrics, Genetics, Public health, and experts working in the field of rare diseases, to finalize the study proposal, data collection tools, and developing protocols for data entry and quality check. Data governance is overseen by ICMR, which ensures centralized data stewardship. Site investigators may access anonymized data for research purposes with appropriate approvals.

Web platform: The registry web portal consists of a frontend and backend. The platform’s frontend is developed using a robust high-level Python framework, known for encouraging rapid development and producing a clean and pragmatic design and backend is developed using object-relation database system. Open-source technologies have been opted in order to facilitate dynamic evolution of the registry in order to interoperate with other data collection sources. The optimal selection of frontend and backend technologies offers several features that enable meticulous scaling and efficient data workload management. The portal inherently offers capacity to collect longitudinal data of the patient through follow-up at 6-month or annual intervals depending on disease type and availability of patient data, with a very user-friendly interface enabling users from different backgrounds to access the services. The registry portal is scalable with integration capabilities with other data sets and other national and international data collection platforms. The data reporting and analysis engine of the portal has been designed in such a way to allow routine reports as well as raw data access to different stakeholders for in-depth analysis/modelling.

Data Safety and Anonymity: The access to the registry portal is through strict authentication, authorization and accounting principles. The different stakeholders can only gain access thorough pre-defined user credentials followed by enforced authorization cheeks i.e. only site-specific data access to each stakeholder. The data exports are strictly controlled and completely anonymized. Regular data backups are taken and stored on separate machines following the typical standard operating procedures for the data backups. The web portal had also undergone a mandatory security audit and has been certified as safe to host for data collection.

The continuity and quality of data entered on the registry portal are significantly impacted by the inflow and outflow of the project staff involved in data entry process at different centres. To overcome this hurdle, group and individual training sessions are conducted for the new project staff as per the need. Regular trouble shooting services are provided by the ICMR data center team for smooth functioning of the registry portal. The site principal investigators (PIs) also ensure that the new staff is familiarized with the registry upon joining. This orientation and guidance help the staff to effectively contribute to the registry by entering correct and quality data in the registry.

As of February 2025, a total of 15,369 patients have been enrolled in the registry for the 6 disorder groups, which encompass 231 rare diseases. The regional distribution depicted that North India accounted for the highest proportion (5229, 34%) of patients enrolled in the registry, followed by South India (4464,29%), Central India (2161, 14%), East India (1708, 11%), North-East India (1094, 7%) and least from West India (713, 5%). The state-wise distribution of patients as per their residential address has been shown in Fig. 4.

The average diagnostic delay for Storage disorders, IEM, Skeletal dysplasia, Dystrophinopathy, Limb Girdle Muscular Dystrophy, Thalassemia, Sickle Cell Disease has been found to be 2.39 ± 4.33 years (Median: 1 year). Figure 6 reveals that nearly half of the patients (47.14%) were diagnosed with one of the rare diseases within one year of symptom onset. The highest number of patients enrolled are for Neuromuscular disorders (n = 6307), followed by Thalassemia (n = 3276), Storage disorders (n = 1632) and Bleeding disorders (n = 1399). The detailed disease-wise enrollments in the registry are shown in Table 3.

Apart from the above-mentioned data, information on clinical presentation, diagnosis, management and quality of life specific to the disease condition is available in the registry, but it is beyond the scope of this paper and will be presented in separate papers on disease-specific analyses.

This study provides the first national-level insights into rare disease demographics, diagnostic timelines, and clinical representation in India using real-world data from the NRROID. The setting up of the registry marked a significant step and enabled a structured approach towards collecting, analyzing and comprehending the landscape of rare diseases in India. This study outlines the process of establishing a hospital-based rare disease registry and summarizes early demographic and diagnostic trends. Currently, the registry database consists of 15,369 rare disease patients from across the nation. This database not only aims to enhance clinical understanding and expertise but also informs healthcare policies and improve the access to diagnostic, management and treatment options for the affected patients. The registry also serves as a resource for identifying patient pools for clinical trials and estimating treatment costs for diseases under consideration by NPRD. The regional distribution of enrolled patients depicts a higher burden of rare disorders in North India. However, this concentration may be due to the disproportionate number of contributing centres in this region, as compared to other regions of India. This predominance of centres in North India could be the reason for the skewed regional distribution of patients. Our registry has reported a male predominance (75%) among Indian rare disease patients. Similarly, China’s hospital-based national rare disease registry system reported burden of rare diseases to be higher among males (55.92%). (16) In contrast, findings from the registries of England, Mexico and Tuscany have reported a female predominance with 55%, 73.61% and 54.1%, respectively. (17, 18, 19) In India, social and cultural norms often result in diagnostic bias and gender bias in health-seeking behavior enhance this disparity. Additionally, certain rare diseases, particularly X-linked and few metabolic or neuromuscular disorders, are more prevalent in males, which may also contribute to the observed skewness. The NRROID has reported that the majority of patients (81.15%) are under the age of 18 years, whereas registries from China, England, and Mexico have reported that patients under 18 years account for 36.07%, 25.2% and 33.33%, respectively. (16, 17, 18) Nearly half of the rare disease patients enrolled in the Indian NRROID were diagnosed within one year of symptom onset. This data aligns with the findings of the Spanish Rare Diseases Patient Registry, which reports that 43.6% of patients experienced a delay of less than 1 year in diagnosis. (20) Despite this, a significant portion of patients still experience a prolonged delay in diagnosis since many rare disorders have widely varied phenotypical manifestations.

Countries like England, Italy, and Australia have established population-based rare disease registries as they have centralized data infrastructures, robust national health systems, integrated electronic health records and mandatory reporting mechanisms. (17, 19, 21) In contrast, India lacks a centralized healthcare system and has limited digital integration across public and private sectors. Unlike other countries, India does not follow a unified disease classification and coding system, such as Orpha codes or International Classification of Diseases (ICD) coding, which enable uniform classification and identification of rare diseases. Additionally, there is no mandatory reporting system as not all rare disease diagnoses are systematically reported to any central authority. Low health literacy and stigma surrounding genetic disorders contribute to underdiagnosis and underreporting in India. Hence, due to such limitations, at present it is difficult to establish a population-based rare disease registry in India. Newborn screening data for a limited number of disorders can be a good resource but as it is still not a national program and few states are offering, the data will not be representative for the whole country. We are presently looking at the possibility of extracting data on the carrier status for rare disorders and extrapolating the number of affected individuals from the “Genome India Project” recently completed and preliminary results published (22)

Establishing India's first National Rare Disease Registry is a crucial step towards addressing all the challenges faced by rare disease patients in India. The Registry database could be leveraged as a comprehensive resource for developing targeted therapies, improving treatment protocols, and formulating effective public health policies. As NRROID continues to expand and evolve, it has the potential to become a cornerstone that could significantly benefit the lives of rare disease patients in India. This paper offers an overview of the experiences and challenges in setting up a National Rare Disease Registry and the registry provides foundational insights for guiding rare disease research, policy development, and clinical practice in India and similar healthcare settings.