Design, Development, and Implementation of India’s National Registry for Rare and Other Inherited Disorders

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These diseases are often complex and challenging to diagnose and treat, significantly impacting lives of those affected and their families. Limitation in the knowledge that persists for most rare diseases is due to the dearth of reliable data on rare diseases in India. A patient registry is a powerful tool for systematically collecting data and creating a database necessary for informing healthcare policy and its execution. The National Registry for Rare and Other Inherited Disorders (NRROID) is a prospective hospital-based study initiated by the Indian Council of Medical Research in 2019 currently at 23 centres in India, to gather comprehensive data on selected rare diseases, including natural history, treatment, and disease outcomes, and to create a database to support further research and assist in the development of policies aimed at improving healthcare outcomes for rare disease patients. Currently, six broad groups of disorders, namely, storage disorders, inborn errors of metabolism (small molecule), skeletal dysplasias, primary immunodeficiencies, neuromuscular disorders, and hematological disorders have been included for reporting in the registry. Presently, NRROID provides valuable data related to demography, clinical features, diagnosis, management, and some other aspects of rare diseases. Results : Till February 2025, registry enrolled 15,369 patients under the 6 broad rare disease groups encompassing 231 rare diseases. Regional distribution depicts that the highest number of rare disease patients enrolled are from North India (34%) followed by South India (29%). Neuromuscular disorders (6307) account for the highest number of patient enrollments, followed by Thalassemia (3276) and Storage disorders (1632). A significant predominance of male patients (75%) has been reported in the registry, and the majority of patients (81.15%) fall in the pediatric age group under 18 years of age. Conclusion : This article summarizes the implementation of India’s first national rare disease registry and highlights key demographic and clinical trends. The NRROID provides foundational data to inform policy, research, and clinical care for rare disease patients in India. Rare Disease Hospital-Based Registry Data Quality India Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 BACKGROUND 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. Figure 1. Challenges surrounding Rare Diseases that lead to difficulty in diagnosis & treatment METHODS Study Design Prospective hospital-based observational study. Study Setting The study is currently ongoing at 23 centers across the country as shown in Fig. 2. The centres were selected based on the site-selection criteria mentioned later, which was assessed based on the information provided by all centres. These centers are a mix of government hospitals and private institutions that provide specialized diagnostic facilities and care to rare disease patients. Figure 2. Centres contributing to the registry Rare Disease Selection Criteria for inclusion in the registry: After expert consultation, it was decided to include a group of rare disorders as mentioned in Table 1 , which primarily included relatively common and treatable or potentially treatable disorders. The majority of these rare disorders are included in the National Policy for Rare Diseases (NPRD, 2021). Table 1 Group of Rare Disorders included in the registry Group I Storage disorders (Lysosomal Storage Disorders & Glycogen Storage Disorders) Gaucher’s disease, Mucopolysaccharidosis (MPS) I, MPS II, MPS IV, MPS VI, Pompe’s disease, Fabry’s disease, Hereditary fructose intolerance, Glycogen Storage Disorders (I & III) Group II Small Molecule Inborn Errors of Metabolisms Phenylketonuria, Homocystinuria, Tyrosinemia, Citrullinemia, Ornithine transcarbamylase deficiency, Maple syrup urine disease, Methylmalonic acidemia, Glutaric aciduria type I, Galactosemia and related disorders Group III Hematological Disorders Hemophilias, Thalassemias, Sickle cell Disease Group IV Skeletal dysplasias Osteogenesis Imperfecta, Achondroplasia Group V Primary Immune deficiencies Severe combined immunodeficiency, Pan hypogammaglobulinemia, Common variable immunodeficiency, X-linked agammaglobulinemia, Chronic Granulomatous Disease Group VI Neuromuscular Disorders Duchenne muscular dystrophy, Spinal Muscular Atrophy, Limb-girdle muscular dystrophies Inclusion Criteria Any patient irrespective of age and sex with a confirmed diagnosis of a rare disease falling under one of the above-mentioned disease categories is included in the registry. The diagnosis of a rare disease is confirmed based on the diagnostic criteria added as supplementary material. Initiation of the Registry and Identification of Various Stakeholders 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: Availability of Clinical Geneticist / Interested Pediatrician Reasonably high number of cases diagnosed Availability of basic Diagnostic & Counseling facilities 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. How is Patient Data Collected in the Registry? Development of Study Tools and Identifying Data Variables It becomes essential for any patient registry to define the data elements and standardize data collection for rare diseases to maintain uniformity in the dataset. ( 14 ) While setting up the registry, one of the important tasks was the finalization of disease-specific case record forms and the selection of only the necessary common data elements (CDE), which would provide an opportunity to fill in the knowledge gap and assist healthcare providers in developing a better understanding of rare diseases. In this registry, patient information is collected in two parts: common socio-demographic information, and in the second part, clinical features, family history including pedigrees, consanguinity, diagnostic delay, molecular, hematological and biochemical diagnostic tests, treatment details- definitive and supportive, quality of life and functionality indicators and expenditure sources for each disease-specific case record form. Development of a Safe and Secure Web Portal for the Registry 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. How is Data Quality Ensured in the Registry? Ensuring the completeness, accuracy, and timeliness of data collected is essential for any registry. Hence, it becomes vital to devise a robust and effective Quality assurance and Quality check (QA/QC) process. The data quality is ensured at four levels in the registry, which is depicted in Fig. 3: I- e-form, II- Site PIs, III- Nodal Centres and IV- ICMR. Various checks and validations have been implemented at the electronic data entry level, including mandatory fields, numeric value ranges, character limits, specific format entries (such as calendars, numbers, multiple and single select options, and dropdown menus), to ensure that complete and correct data is entered. An error pop-up is displayed on the screen if any field is not filled as per the validation applied and further data entry is not possible without correction of the error. Standardized Standard Operating Procedures (SOPs) were developed and regular centralized and site-specific training sessions are held to ensure data entry consistency across centers. Some of the participating centres have been designated as nodal centers (for respective disease groups) to check essential and mandatory fields of each rare disease form. For this, a QA/QC web portal is developed to ensure a continuous QA/QC process. They are provided with login credentials for conducting QA/QC on the anonymized data shared by ICMR on the web portal. The QA/QC result becomes visible simultaneously to all the participating sites as QA/QC pass or fail, along with feedback for the ones that have failed in the quality check to improve the accuracy and quality of data. All the sites can resubmit a corrected entry based on the feedback received from the nodal centres. The ICMR team shares monthly and weekly reports with all the sites individually, highlighting the completion status of disease-wise forms, and informing them about their performance during the past month. A visual dashboard is also available to the sites to see their performance. Figure 3: QA/QC performed at four levels Maintaining Data Quality: Regular training among the dynamic pool of human resource 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. Optimizing Registry Performance: Developing a Monitoring and Feedback System Role and Responsibilities of the Technical Advisory Group (TAG) It is crucial to establish a Technical Advisory Group (TAG), a group of experts whose responsibility should be to review the progress of the registry regularly. The TAG experts provide critical inputs and expertise to improve the functioning of the registry. It is important to have experts from diverse fields like pediatrics, genetics, public health, and government policy makers for their unique perspectives. The annual reports from the registry are evaluated during yearly meetings of the Technical Advisory Group (TAG) and investigating teams. Alignment of the Rare Disease Registry with National Policies and Initiatives The policy on rare diseases is in an evolving phase. The registry mandatorily updates itself with the evolving policy. To date the Government of India has designated 13 institutes from across the country as Centres of Excellence (CoE) for Rare Diseases. These CoEs are equipped with specialized facilities for the diagnosis, counseling, treatment and prevention of rare diseases. Their main responsibility is to provide diagnostic and treatment facilities to rare disease patients apart from education and training to healthcare providers at all levels of healthcare, perform screening and diagnosis among pregnant women and neonates, provide treatment for rare diseases, and conduct research for developing low-cost diagnostics & therapeutics. ( 10 ) These CoEs manage a significant number of rare disease patients, and have been mandated to contribute to the registry. The registry also aligns itself by including new rare disorders to the list as and when they become notifiable under the NPRD. RESULTS 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. Figure 4. State-wise Distribution of Rare Disease Patients as per their residential address Table 2 Demographic and Genetic Characteristics of Rare Disease Patients Variables* N(%) Religion Hindu 10618 (79.63) Muslim 1820 (13.65) Sikh 204 (1.53) Christian 157 (1.18) Others 536 (4.02) Grand Total 13335 Monthly Family Income (Rs.)** 126360 147 (2.24) Total 6572 Positive Family History of Rare Disorders No 7914 (79.18) Yes 2081 (20.82) Total 9995 Family Members affected by Rare Disorders Sibling 1133 (59.23) Uncle 381 (19.92) Cousin 196 (10.24) Grandmother 71 (3.71) Mother 59 (3.08) Father 42 (2.20) Grandfather 26 (1.36) Aunt 5 (0.26) Total 1913 Consanguinity No 6351 (76.94) Yes 1904 (23.06) Total 8255 Degree of Consanguinity First 33 (5.12) Second 96 (14.91) Third 441 (68.48) Fourth 42 (6.52) Fifth and more 32 (4.97) Total 644 *Since these variables are non-mandatory, patient record numbers vary across variables based on data availability **Monthly income categories adapted from Modified Kuppuswamy Scale 2018 ( 15 ) Figure 6. Diagnostic delay among rare disease patients *Storage disorders, Inborn errors of metabolism, Skeletal dysplasia, Dystrophinopathy, Limb Girdle Muscular Dystrophy, Thalassemia, Sickle Cell Disease Table 3 Disease-wise enrollment of patients in the registry Disorder Groups No. of patients enrolled (N = 15369) Neuromuscular Disorders 6307 Thalassemia 3276 Storage Disorders 1632 Bleeding Disorders 1399 Inborn errors of metabolism 938 Primary Immune deficiencies 719 Sickle Cell Disease 679 Skeletal dysplasias 419 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. DISCUSSION 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 ) Challenges and Limitations: This registry was established to overcome the lack of a comprehensive rare disease patient database in our country. However, as a hospital-based registry, it is subject to some limitations. The major challenge of this hospital-based registry is the estimation of the true prevalence of rare diseases in our country. Thus, those patients who have not visited these specialized institutes, or those with no access to healthcare services have not been enrolled in the registry at present. The reporting of rare diseases is limited to common and potentially manageable rare diseases. Most rare diseases suffer from challenge of underdiagnosis; mostly because of under recognition, early death before a correct diagnosis and poor access to adequate diagnostic facilities in each state. Though this leads to the non-reporting of several diseases, however, it ensures good quality data that helps as policy aid for allocating resources helps clinicians in decision making and stimulates further research in drugs and diagnostics. Follow-up is currently limited to certain disorders as a lot of time was spent on setting up the registry. Following up the patients with no specific treatment being offered is a big challenge. Since the dataset includes both mandatory and non-mandatory variables, not all patient information is consistently recorded across all variables. As a result, the number of available records varies from one variable to another. Achievements of the registry : The Ministry of Health and Family Welfare is regularly updated about the number of patients enrolled under various categories of rare diseases and their sub-types. The registry helps to bring visibility through a national register to rare disease patients by identifying the geographical distribution of patients suffering from rare diseases. This registry establishes a common platform for communication and discussion concerning rare diseases between specialists from different institutes. It also creates a network of diagnostic facilities available at different institutes for quick referral and increasing the diagnosis rate for rare diseases. This registry acts as a medium for creating awareness and bridging the knowledge gap among healthcare providers, rare disease patients, their families, the general public, and patient support groups about rare diseases, and the need to support rare disease patients. Way Forward: As part of the ongoing efforts to increase visibility and awareness about rare diseases among healthcare providers, policymakers, patients, caregivers, and the general public, it is planned to develop a national rare disease information portal. A new integrated and centralized National Rare Disease Portal will be developed, hence creating an easy path for patients, their families, clinicians, researchers, sponsors, industry and donors to get relevant information and updates about the rare diseases, COEs, and new advances. This would ensure that all the stakeholders are informed and engaged in the decision-making process, leading to improved patient care. The registry will keep updating itself to keep alignment between diseases added in NPRD and new centres of excellence identified. Also, it is planned to incorporate disease-specific follow-up forms on the registry portal to capture data on the progression and outcome of diseases, and response to various treatment therapies as well as the expenditure details. Conclusion 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. Abbreviations CDE Common Data Elements COE Centre of Excellence EOI Expression of Interest ICD International Classification of Diseases ICMR Indian Council of Medical Research MoHFW Ministry of Health and Family Welfare NPRD National Policy for Rare Disease NPTRD National Policy for Treatment of Rare Diseases NRROID National Registry for Rare and Other Inherited Disorders OPD Out Patient Department PI Principal Investigator PII Personnel Identifier Information QA Quality Assurance QC Quality Check SOP Standard Operating Procedures TAG Technical Advisory Group WHO World Health Organization Declarations Ethical Approval and consent to participate: Ethical Approval has been obtained from the Institutional Ethics Committees of each of the institutes that are a part of the registry. Written informed consent is taken before enrolling the rare disease patient into the registry, and a participant information sheet is also provided to each participant. Patient data privacy and confidentiality is maintained. All the registry data is stored securely at the study sites with password-protected systems. The physical case record forms are stored in a separate locked cabinet. Consent for Publication: Written consent was taken from all the participants before enrolling them into the registry. Availability of data and materials: The datasets generated and/or analyzed during the current study are available from the ICMR upon reasonable request. Competing interests: The authors declare that they have no competing interests. Source of funding: This registry is being funded by the Indian Council of Medical Research since 2019 (CAR-2019-00-00002) Authors' contributions: The authors A, AS, RR, AG and PV are the employees of the funding agency and have been involved in the study designing, hosting the data management portal, data management and data quality, data cleaning, analysis, preparation and revision of the manuscript. The remaining authors are the principle investigators of the contributing institutes, who are involved in collecting patient data and their enrollment into the registry, ensuring data quality for their respective sites and critical review of the manuscript. The NRROID Registry Group is involved in the data collection and patient enrollment. All authors have read and approved the final manuscript. Acknowledgements: NRROID Registry Group: Bhavna Dhingra, Mukul Gupta, Tulika Seth, Ravi Ranjan, Biswaroop Chakrabarty, Prashant Jauhari, Hima Bindu Vipparthi, Venkataraman Viswanathan, Maya Thomas, Sangeetha Yoganathan, Prince Jacob, Sumaiya Kausar S. Kalaigar, Navyashree Mugur Jagadeesh, Sunil Kumar Polipalli, Seena Vengalil, Shagun Aggarwal, Ankur Agarwal, Mayank Nilay, Umesh Shukla, Deepti Suri, Vignesh Pandiarajan, Ankur Jindal, Naveen Sankhyan, Renu Suthar, Jitendra Sahu, Savita Verma Atri, Arushi Saini, Reena Das, Jasmina Ahluwalia, Amita Trehan, Deepak Bansal, Rakesh Pilania, Alka Khadwal, Arihant Jain, Kausik Mandal, Amita Moirangthem, VK Khanna, Praveen Kumar, Manas Kalra, Sudha Kohli. The authors also thank All India Institute of Medical Sciences, Jodhpur, Center for Human Genetics, Bangalore, Institute of Child Health and Hospital for Children, Chennai, Institute of Post-Graduate Medical Education and Research, Kolkata, King Edward Memorial Hospital, Mumbai, and Sree Avittam Thirunal Hospital, Trivandrum, Kerala for their contribution to the registry. References Ferreira CR. The burden of rare diseases. American journal of medical genetics Part A. 2019 Jun;179(6):885-92. 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Nat Genet 57, 767–773 (2025). https://doi.org/10.1038/s41588-025-02153-x Supplementary Files SupplementaryMaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 12 Nov, 2025 Reviewers invited by journal 12 Nov, 2025 Editor invited by journal 18 Jun, 2025 Editor assigned by journal 18 Jun, 2025 First submitted to journal 17 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":63959,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChallenges surrounding Rare Diseases that lead to difficulty in diagnosis \u0026amp; treatment\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/96bde76e81cab3c6ea0fbc1f.png"},{"id":96709411,"identity":"579dc5d0-e054-4583-85ff-e03e7b068cd9","added_by":"auto","created_at":"2025-11-25 10:08:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":221487,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentres contributing to the registry\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/fdf1421976c03771b30d1d8c.png"},{"id":96709488,"identity":"d3f2ab37-38db-4c8b-9e27-c13c556369d7","added_by":"auto","created_at":"2025-11-25 10:09:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":17993,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eQA/QC performed at four levels\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/82df3f9dd43d780b54874e6c.png"},{"id":96710323,"identity":"6cea9d7f-994b-4e7c-a21b-d250c2cf619f","added_by":"auto","created_at":"2025-11-25 10:10:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":374666,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eState-wise Distribution of Rare Disease Patients as per their residential address\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/0296d3b53e018c5c36bb5847.png"},{"id":96709469,"identity":"b8207538-222d-40b5-b664-1d9f9c79e747","added_by":"auto","created_at":"2025-11-25 10:09:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":70832,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of Rare Disease Patients by Age\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/c7028d0ec196d198710b281d.png"},{"id":96654405,"identity":"f20e8742-fb6e-414f-a249-0fb36fcf9e1c","added_by":"auto","created_at":"2025-11-24 16:43:40","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":12273,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDiagnostic delay among rare disease patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e*Storage disorders, Inborn errors of metabolism, Skeletal dysplasia, Dystrophinopathy, Limb Girdle Muscular Dystrophy, Thalassemia, Sickle Cell Disease\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/2d620bb156e8a7565171082d.png"},{"id":96712860,"identity":"f2cf39f2-8249-4031-b697-92c3155d5197","added_by":"auto","created_at":"2025-11-25 10:17:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2544106,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/0a177c3c-a4f0-409b-ab3a-546146d619ff.pdf"},{"id":96709236,"identity":"f82e881e-2889-42d9-b440-b6c719137d10","added_by":"auto","created_at":"2025-11-25 10:08:20","extension":"docx","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":1354858,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6918670/v1/d74dba273efa7b405dc0c527.docx"}],"financialInterests":"","formattedTitle":"Design, Development, and Implementation of India’s National Registry for Rare and Other Inherited Disorders","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eIt is estimated that there are approximately 7,000\u0026ndash;8,000 rare diseases worldwide. While each rare disease affects a smaller population individually, according to an estimate collectively they impact 3.5\u0026ndash;5.9% of the global population amounting to approximately 400\u0026nbsp;million people globally. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) 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. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) 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). (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Like many other developing countries, currently India does not have a standard definition for rare diseases. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) 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.\u0026nbsp;1. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eRare 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 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). 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. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) 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. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Research on developing new and affordable diagnostic therapies for rare diseases needs to be intensified for ensuring drug accessibility. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) 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. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) 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. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eA 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. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) 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. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) There can be various contexts for each country.\u003c/p\u003e\u003cp\u003eThe ICMR initiated the \u0026ldquo;National Registry for Rare and Other Inherited Disorders (NRROID)\u0026rdquo; 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.\u003c/p\u003e\u003cp\u003eThis 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.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 1. Challenges surrounding Rare Diseases that lead to difficulty in diagnosis \u0026amp; treatment\u003c/b\u003e\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003cp\u003eProspective hospital-based observational study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStudy Setting\u003c/strong\u003e\u003cp\u003eThe study is currently ongoing at 23 centers across the country as shown in Fig.\u0026nbsp;2. The centres were selected based on the site-selection criteria mentioned later, which was assessed based on the information provided by all centres. These centers are a mix of government hospitals and private institutions that provide specialized diagnostic facilities and care to rare disease patients.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 2. Centres contributing to the registry\u003c/b\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eRare Disease Selection Criteria for inclusion in the registry:\u003c/h2\u003e\u003cp\u003eAfter expert consultation, it was decided to include a group of rare disorders as mentioned in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, which primarily included relatively common and treatable or potentially treatable disorders. The majority of these rare disorders are included in the National Policy for Rare Diseases (NPRD, 2021).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGroup of Rare Disorders included in the registry\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup I\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStorage disorders (Lysosomal Storage Disorders \u0026amp; Glycogen Storage Disorders)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGaucher\u0026rsquo;s disease, Mucopolysaccharidosis (MPS) I, MPS II, MPS IV, MPS VI, Pompe\u0026rsquo;s disease, Fabry\u0026rsquo;s disease, Hereditary fructose intolerance, Glycogen Storage Disorders (I \u0026amp; III)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGroup II\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSmall Molecule\u003c/p\u003e\u003cp\u003eInborn Errors of Metabolisms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePhenylketonuria, Homocystinuria, Tyrosinemia, Citrullinemia, Ornithine transcarbamylase deficiency, Maple syrup urine disease, Methylmalonic acidemia, Glutaric aciduria type I, Galactosemia and related disorders\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGroup III\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHematological Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHemophilias, Thalassemias, Sickle cell Disease\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGroup IV\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSkeletal dysplasias\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOsteogenesis Imperfecta, Achondroplasia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGroup V\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePrimary Immune deficiencies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSevere combined immunodeficiency, Pan hypogammaglobulinemia, Common variable immunodeficiency, X-linked agammaglobulinemia, Chronic Granulomatous Disease\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGroup VI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeuromuscular Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDuchenne muscular dystrophy, Spinal Muscular Atrophy, Limb-girdle muscular dystrophies\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eInclusion Criteria\u003c/strong\u003e\u003cp\u003eAny patient irrespective of age and sex with a confirmed diagnosis of a rare disease falling under one of the above-mentioned disease categories is included in the registry. The diagnosis of a rare disease is confirmed based on the diagnostic criteria added as supplementary material.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInitiation of the Registry and Identification of Various Stakeholders\u003c/h3\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\u003cp\u003eSite-selection Criteria:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAvailability of Clinical Geneticist / Interested Pediatrician\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eReasonably high number of cases diagnosed\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAvailability of basic Diagnostic \u0026amp; Counseling facilities\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eAfter 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.\u003c/p\u003e\n\u003ch3\u003eHow is Patient Data Collected in the Registry?\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eDevelopment of Study Tools and Identifying Data Variables\u003c/h2\u003e\u003cp\u003eIt becomes essential for any patient registry to define the data elements and standardize data collection for rare diseases to maintain uniformity in the dataset. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) While setting up the registry, one of the important tasks was the finalization of disease-specific case record forms and the selection of only the necessary common data elements (CDE), which would provide an opportunity to fill in the knowledge gap and assist healthcare providers in developing a better understanding of rare diseases. In this registry, patient information is collected in two parts: common socio-demographic information, and in the second part, clinical features, family history including pedigrees, consanguinity, diagnostic delay, molecular, hematological and biochemical diagnostic tests, treatment details- definitive and supportive, quality of life and functionality indicators and expenditure sources for each disease-specific case record form.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDevelopment of a Safe and Secure Web Portal for the Registry\u003c/h3\u003e\n\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eWeb platform\u003c/span\u003e: The registry web portal consists of a frontend and backend. The platform\u0026rsquo;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.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eData Safety and Anonymity\u003c/span\u003e: 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.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eHow is Data Quality Ensured in the Registry?\u003c/h2\u003e\u003cp\u003eEnsuring the completeness, accuracy, and timeliness of data collected is essential for any registry. Hence, it becomes vital to devise a robust and effective Quality assurance and Quality check (QA/QC) process. The data quality is ensured at four levels in the registry, which is depicted in Fig.\u0026nbsp;3: I- e-form, II- Site PIs, III- Nodal Centres and IV- ICMR. Various checks and validations have been implemented at the electronic data entry level, including mandatory fields, numeric value ranges, character limits, specific format entries (such as calendars, numbers, multiple and single select options, and dropdown menus), to ensure that complete and correct data is entered. An error pop-up is displayed on the screen if any field is not filled as per the validation applied and further data entry is not possible without correction of the error. Standardized Standard Operating Procedures (SOPs) were developed and regular centralized and site-specific training sessions are held to ensure data entry consistency across centers.\u003c/p\u003e\u003cp\u003eSome of the participating centres have been designated as nodal centers (for respective disease groups) to check essential and mandatory fields of each rare disease form. For this, a QA/QC web portal is developed to ensure a continuous QA/QC process. They are provided with login credentials for conducting QA/QC on the anonymized data shared by ICMR on the web portal. The QA/QC result becomes visible simultaneously to all the participating sites as QA/QC pass or fail, along with feedback for the ones that have failed in the quality check to improve the accuracy and quality of data. All the sites can resubmit a corrected entry based on the feedback received from the nodal centres. The ICMR team shares monthly and weekly reports with all the sites individually, highlighting the completion status of disease-wise forms, and informing them about their performance during the past month. A visual dashboard is also available to the sites to see their performance.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 3: QA/QC performed at four levels\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMaintaining Data Quality: Regular training among the dynamic pool of human resource\u003c/h3\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003ch3\u003eOptimizing Registry Performance: Developing a Monitoring and Feedback System\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eRole and Responsibilities of the Technical Advisory Group (TAG)\u003c/h2\u003e\u003cp\u003eIt is crucial to establish a Technical Advisory Group (TAG), a group of experts whose responsibility should be to review the progress of the registry regularly. The TAG experts provide critical inputs and expertise to improve the functioning of the registry. It is important to have experts from diverse fields like pediatrics, genetics, public health, and government policy makers for their unique perspectives. The annual reports from the registry are evaluated during yearly meetings of the Technical Advisory Group (TAG) and investigating teams.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eAlignment of the Rare Disease Registry with National Policies and Initiatives\u003c/h2\u003e\u003cp\u003eThe policy on rare diseases is in an evolving phase. The registry mandatorily updates itself with the evolving policy. To date the Government of India has designated 13 institutes from across the country as Centres of Excellence (CoE) for Rare Diseases. These CoEs are equipped with specialized facilities for the diagnosis, counseling, treatment and prevention of rare diseases. Their main responsibility is to provide diagnostic and treatment facilities to rare disease patients apart from education and training to healthcare providers at all levels of healthcare, perform screening and diagnosis among pregnant women and neonates, provide treatment for rare diseases, and conduct research for developing low-cost diagnostics \u0026amp; therapeutics. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) These CoEs manage a significant number of rare disease patients, and have been mandated to contribute to the registry. The registry also aligns itself by including new rare disorders to the list as and when they become notifiable under the NPRD.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAs 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.\u0026nbsp;4.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 4. State-wise Distribution of Rare Disease Patients as per their residential address\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and Genetic Characteristics of Rare Disease Patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN(%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eReligion\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHindu\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10618 (79.63)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMuslim\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1820 (13.65)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSikh\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e204 (1.53)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChristian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e157 (1.18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e536 (4.02)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrand Total\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13335\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMonthly Family Income (Rs.)**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;6323\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e962 (14.64)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6327\u0026ndash;18949\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2911 (44.29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18953\u0026ndash;31589\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1419 (21.59)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e31591\u0026ndash;47262\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e565 (8.60)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e47266\u0026ndash;63178\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e292 (4.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e63182\u0026ndash;126356\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e276 (4.20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;126360\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e147 (2.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6572\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePositive Family History of Rare Disorders\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7914 (79.18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2081 (20.82)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9995\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFamily Members affected by Rare Disorders\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSibling\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1133 (59.23)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUncle\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e381 (19.92)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCousin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e196 (10.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrandmother\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71 (3.71)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMother\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (3.08)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFather\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (2.20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrandfather\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (1.36)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAunt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (0.26)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1913\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConsanguinity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6351 (76.94)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1904 (23.06)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8255\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDegree of Consanguinity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (5.12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecond\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 (14.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThird\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e441 (68.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFourth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (6.52)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFifth and more\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (4.97)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e644\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003e*Since these variables are non-mandatory, patient record numbers vary across variables based on data availability\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e**Monthly income categories adapted from Modified Kuppuswamy Scale 2018\u003c/em\u003e (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 6. Diagnostic delay among rare disease patients\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e*Storage disorders, Inborn errors of metabolism, Skeletal dysplasia, Dystrophinopathy, Limb Girdle Muscular Dystrophy, Thalassemia, Sickle Cell Disease\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDisease-wise enrollment of patients in the registry\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisorder Groups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo. of patients enrolled\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;15369)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuromuscular Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThalassemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3276\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStorage Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1632\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBleeding Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1399\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInborn errors of metabolism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e938\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary Immune deficiencies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e719\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSickle Cell Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e679\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkeletal dysplasias\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e419\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe 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\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.33 years (Median: 1 year). Figure\u0026nbsp;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\u0026thinsp;=\u0026thinsp;6307), followed by Thalassemia (n\u0026thinsp;=\u0026thinsp;3276), Storage disorders (n\u0026thinsp;=\u0026thinsp;1632) and Bleeding disorders (n\u0026thinsp;=\u0026thinsp;1399). The detailed disease-wise enrollments in the registry are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eApart 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.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis 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\u0026rsquo;s hospital-based national rare disease registry system reported burden of rare diseases to be higher among males (55.92%). (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) In contrast, findings from the registries of England, Mexico and Tuscany have reported a female predominance with 55%, 73.61% and 54.1%, respectively. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) 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. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) 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. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Despite this, a significant portion of patients still experience a prolonged delay in diagnosis since many rare disorders have widely varied phenotypical manifestations.\u003c/p\u003e\u003cp\u003eCountries 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. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) 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 \u0026ldquo;Genome India Project\u0026rdquo; recently completed and preliminary results published (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eChallenges and Limitations:\u003c/h2\u003e\u003cp\u003eThis registry was established to overcome the lack of a comprehensive rare disease patient database in our country. However, as a hospital-based registry, it is subject to some limitations.\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe major challenge of this hospital-based registry is the estimation of the true prevalence of rare diseases in our country. Thus, those patients who have not visited these specialized institutes, or those with no access to healthcare services have not been enrolled in the registry at present.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe reporting of rare diseases is limited to common and potentially manageable rare diseases. Most rare diseases suffer from challenge of underdiagnosis; mostly because of under recognition, early death before a correct diagnosis and poor access to adequate diagnostic facilities in each state. Though this leads to the non-reporting of several diseases, however, it ensures good quality data that helps as policy aid for allocating resources helps clinicians in decision making and stimulates further research in drugs and diagnostics.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eFollow-up is currently limited to certain disorders as a lot of time was spent on setting up the registry. Following up the patients with no specific treatment being offered is a big challenge.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eSince the dataset includes both mandatory and non-mandatory variables, not all patient information is consistently recorded across all variables. As a result, the number of available records varies from one variable to another.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAchievements of the registry\u003c/span\u003e:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe Ministry of Health and Family Welfare is regularly updated about the number of patients enrolled under various categories of rare diseases and their sub-types.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe registry helps to bring visibility through a national register to rare disease patients by identifying the geographical distribution of patients suffering from rare diseases.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThis registry establishes a common platform for communication and discussion concerning rare diseases between specialists from different institutes.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIt also creates a network of diagnostic facilities available at different institutes for quick referral and increasing the diagnosis rate for rare diseases.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThis registry acts as a medium for creating awareness and bridging the knowledge gap among healthcare providers, rare disease patients, their families, the general public, and patient support groups about rare diseases, and the need to support rare disease patients.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eWay Forward:\u003c/h2\u003e\u003cp\u003eAs part of the ongoing efforts to increase visibility and awareness about rare diseases among healthcare providers, policymakers, patients, caregivers, and the general public, it is planned to develop a national rare disease information portal. A new integrated and centralized National Rare Disease Portal will be developed, hence creating an easy path for patients, their families, clinicians, researchers, sponsors, industry and donors to get relevant information and updates about the rare diseases, COEs, and new advances. This would ensure that all the stakeholders are informed and engaged in the decision-making process, leading to improved patient care.\u003c/p\u003e\u003cp\u003eThe registry will keep updating itself to keep alignment between diseases added in NPRD and new centres of excellence identified. Also, it is planned to incorporate disease-specific follow-up forms on the registry portal to capture data on the progression and outcome of diseases, and response to various treatment therapies as well as the expenditure details.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEstablishing 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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eCDE\u003c/div\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eCommon Data Elements\u003c/div\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eCOE\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eCentre of Excellence\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eEOI\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eExpression of Interest\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eICD\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eInternational Classification of Diseases\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eICMR\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eIndian Council of Medical Research\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eMoHFW\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eMinistry of Health and Family Welfare\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNPRD\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eNational Policy for Rare Disease\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNPTRD\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eNational Policy for Treatment of Rare Diseases\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eNRROID\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eNational Registry for Rare and Other Inherited Disorders\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eOPD\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eOut Patient Department\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003ePI\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003ePrincipal Investigator\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003ePII\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003ePersonnel Identifier Information\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eQA\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eQuality Assurance\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eQC\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eQuality Check\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eSOP\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eStandard Operating Procedures\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eTAG\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eTechnical Advisory Group\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cdiv class=\"SimplePara\"\u003eWHO\u003c/div\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cdiv class=\"SimplePara\"\u003eWorld Health Organization\u003c/div\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003cbr/\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and consent to participate:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthical Approval has been obtained from the Institutional Ethics Committees of each of the institutes that are a part of the registry. Written informed consent is taken before enrolling the rare disease patient into the registry, and a participant information sheet is also provided to each participant. Patient data privacy and confidentiality is maintained. All the registry data is stored securely at the study sites with password-protected systems. The physical case record forms are stored in a separate locked cabinet.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent was taken from all the participants before enrolling them into the registry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the ICMR upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of funding:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis registry is being funded by the Indian Council of Medical Research since 2019 (CAR-2019-00-00002)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors A, AS, RR, AG and PV are the employees of the funding agency and have been involved in the study designing, hosting the data management portal, data management and data quality, data cleaning, analysis, preparation and revision of the manuscript. The remaining authors are the principle investigators of the contributing institutes, who are involved in collecting patient data and their enrollment into the registry, ensuring data quality for their respective sites and critical review of the manuscript. The NRROID Registry Group is involved in the data collection and patient enrollment. All authors have read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNRROID Registry Group:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBhavna Dhingra, Mukul Gupta, Tulika Seth, Ravi Ranjan, Biswaroop Chakrabarty, Prashant Jauhari, Hima Bindu Vipparthi, Venkataraman Viswanathan, Maya Thomas, Sangeetha Yoganathan, Prince Jacob, Sumaiya Kausar S. Kalaigar, Navyashree Mugur Jagadeesh, Sunil Kumar Polipalli, Seena Vengalil, Shagun Aggarwal, Ankur Agarwal, Mayank Nilay, Umesh Shukla, Deepti Suri, Vignesh Pandiarajan, Ankur Jindal, Naveen Sankhyan, Renu Suthar, Jitendra Sahu, Savita Verma Atri, Arushi Saini, Reena Das, Jasmina Ahluwalia, Amita Trehan, Deepak Bansal, Rakesh Pilania, Alka Khadwal, Arihant Jain, Kausik Mandal, Amita Moirangthem, VK Khanna, Praveen Kumar, Manas Kalra, Sudha Kohli.\u003c/p\u003e\n\u003cp\u003eThe authors also thank All India Institute of Medical Sciences, Jodhpur, Center for Human Genetics, Bangalore, Institute of Child Health and Hospital for Children, Chennai, Institute of Post-Graduate Medical Education and Research, Kolkata, King Edward Memorial Hospital, Mumbai, and Sree Avittam Thirunal Hospital, Trivandrum, Kerala for their contribution to the registry.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFerreira CR. The burden of rare diseases. American journal of medical genetics Part A. 2019 Jun;179(6):885-92.\u003c/li\u003e\n \u003cli\u003eVenugopal N, Naik G, Jayanna K, Mohapatra A, Sasinowski FJ, Kartha RV, Rajasimha HK. Review of methods for estimating the prevalence of rare diseases. Rare Dis Orphan Drugs J. 2024;3:5.\u003c/li\u003e\n \u003cli\u003eRajasimha HK, Shirol PB, Ramamoorthy P, Hegde M, Barde S, Chandru V, Ravinandan ME, Ramchandran R, Haldar K, Lin JC, Babar IA. Organization for rare diseases India (ORDI)\u0026ndash;Addressing the challenges and opportunities for the Indian rare diseases\u0026apos; community. Genetics research. 2014 Jan;96:e009.\u003c/li\u003e\n \u003cli\u003eObserver Research Foundation. Rare Diseases in India: \u0026lsquo;Orphan\u0026rsquo; No More?. July 2022. https://www.orfonline.org/research/rare-diseases-in-india-orphan-no-more. Accessed 13 September 2024\u003c/li\u003e\n \u003cli\u003eNguengang Wakap S, Lambert DM, Olry A, Rodwell C, Gueydan C, Lanneau V, Murphy D, Le Cam Y, Rath A. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. European Journal of Human Genetics. 2020 Feb;28(2):165-73.\u003c/li\u003e\n \u003cli\u003eAdachi T, El-Hattab AW, Jain R, Nogales Crespo KA, Quirland Lazo CI, Scarpa M, Summar M, Wattanasirichaigoon D. Enhancing equitable access to rare disease diagnosis and treatment around the world: a review of evidence, policies, and challenges. International journal of environmental research and public health. 2023 Mar 8;20(6):4732.\u003c/li\u003e\n \u003cli\u003eBhattacharya A, Taneja A, SHASHIDHARA L. Rare diseases in India: time for cure-driven policy initiatives and action. Indian Academy of Sciences. 2020 May 25; 118(10):1500-1506.\u003c/li\u003e\n \u003cli\u003eLopes MT, Koch VH, Sarrubbi-Junior V, Gallo PR, Carneiro-Sampaio M. Difficulties in the diagnosis and treatment of rare diseases according to the perceptions of patients, relatives and health care professionals. Clinics. 2018 Apr 5;73:e68.\u003c/li\u003e\n \u003cli\u003eCai X, Genchev GZ, He P, Lu H, Yu G. Demographics, in-hospital analysis, and prevalence of 33 rare diseases with effective treatment in Shanghai. Orphanet Journal of Rare Diseases. 2021 Jun 8;16(1):262.\u003c/li\u003e\n \u003cli\u003eMinistry of Health and Family Welfare. National Policy for Rare Diseases, 2021. March 2021. https://rarediseases.mohfw.gov.in/uploads/Content/1624967837_Final-NPRD-2021.pdf. Accessed 13 September 2024.\u003c/li\u003e\n \u003cli\u003eMorsy A, Lim TO, Varatharajan S, Lim JY. National registries in developing countries: understanding construction challenges and implementation steps. In 2010 5th Cairo International Biomedical Engineering Conference 2010 Dec 16 (pp. 75-78). IEEE.\u003c/li\u003e\n \u003cli\u003eMaria Aziz, Azma J. Khan and Sefia Khan (2021); RARE DISEASE REGISTRIES- PURPOSE, CHALLENGES \u0026amp; SOLUTIONS Int. J. of Adv. Res. 9 (Jan). 1074-1078] (ISSN 2320-5407)\u003c/li\u003e\n \u003cli\u003eTanaka H, Shimaoka M. Challenges associated with delayed definitive diagnosis among Japanese patients with specific intractable diseases: A cross-sectional study. Intractable \u0026amp; Rare Diseases Research. 2023 Nov 30;12(4):213-21.\u003c/li\u003e\n \u003cli\u003eGliklich RE, Dreyer NA, Leavy MB. Rare disease registries. In: Gliklich RE, Dreyer NA, Leavy MB, editors. Registries for evaluating patient outcomes: a user\u0026apos;s guide. 3rd ed. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014. p. [Chapter 20].\u003c/li\u003e\n \u003cli\u003eSaleem SM. Modified Kuppuswamy scale updated for year 2018. Paripex Indian J Res. 2018 Mar;7(3):217-8.\u003c/li\u003e\n \u003cli\u003eGuo J, Liu P, Chen L, Lv H, Li J, Yu W, Xu K, Zhu Y, Wu Z, Tian Z, Jin Y. National Rare Diseases Registry System (NRDRS): China\u0026rsquo;s first nation-wide rare diseases demographic analyses. Orphanet journal of rare diseases. 2021 Dec;16:1-7.\u003c/li\u003e\n \u003cli\u003eThygesen JH, Zhang H, Issa H, Wu J, Hama T, Phiho Gomes AC, Groza T, Khalid S, Lumbers T, Hocaoglu M, Khunti K. A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes. medRxiv. 2023 Oct 13:2023-10.\u003c/li\u003e\n \u003cli\u003eAspiros CE, Gonzaga-Jauregui C. First year results and insights from the Mexican Rare Disease Patient Registry. Rare. 2024 Jan 1;2:100046.\u003c/li\u003e\n \u003cli\u003eBaldacci S, Santoro M, Pierini A, Mezzasalma L, Gorini F, Coi A. Healthcare burden of rare diseases: a population-based study in Tuscany (Italy). International Journal of Environmental Research and Public Health. 2022 Jun 21;19(13):7553.\u003c/li\u003e\n \u003cli\u003eBenito-Lozano J, L\u0026oacute;pez-Villalba B, Arias-Merino G, Posada De la Paz M, Alonso-Ferreira V. Diagnostic delay in rare diseases: data from the Spanish rare diseases patient registry. Orphanet Journal of Rare Diseases. 2022 Nov 17;17(1):418.\u003c/li\u003e\n \u003cli\u003eWalker CE, Mahede T, Davis G, Miller LJ, Girschik J, Brameld K, Sun W, Rath A, Aym\u0026eacute; S, Zubrick SR, Baynam GS. The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. Genetics in Medicine. 2017 May;19(5):546-52.\u003c/li\u003e\n \u003cli\u003eBhattacharyya, C., Subramanian, K., Uppili, B. et al. Mapping genetic diversity with the GenomeIndia project. Nat Genet 57, 767\u0026ndash;773 (2025). https://doi.org/10.1038/s41588-025-02153-x\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Rare Disease, Hospital-Based Registry, Data Quality, India","lastPublishedDoi":"10.21203/rs.3.rs-6918670/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6918670/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Rare diseases are a diverse set of disorders that individually affect a relatively small number of individuals but collectively form an important public health problem globally and in India. These diseases are often complex and challenging to diagnose and treat, significantly impacting lives of those affected and their families. Limitation in the knowledge that persists for most rare diseases is due to the dearth of reliable data on rare diseases in India. A patient registry is a powerful tool for systematically collecting data and creating a database necessary for informing healthcare policy and its execution. The National Registry for Rare and Other Inherited Disorders (NRROID) is a prospective hospital-based study initiated by the Indian Council of Medical Research in 2019 currently at 23 centres in India, to gather comprehensive data on selected rare diseases, including natural history, treatment, and disease outcomes, and to create a database to support further research and assist in the development of policies aimed at improving healthcare outcomes for rare disease patients. Currently, six broad groups of disorders, namely, storage disorders, inborn errors of metabolism (small molecule), skeletal dysplasias, primary immunodeficiencies, neuromuscular disorders, and hematological disorders have been included for reporting in the registry. Presently, NRROID provides valuable data related to demography, clinical features, diagnosis, management, and some other aspects of rare diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Till February 2025, registry enrolled 15,369 patients under the 6 broad rare disease groups encompassing 231 rare diseases. Regional distribution depicts that the highest number of rare disease patients enrolled are from North India (34%) followed by South India (29%). Neuromuscular disorders (6307) account for the highest number of patient enrollments, followed by Thalassemia (3276) and Storage disorders (1632). A significant predominance of male patients (75%) has been reported in the registry, and the majority of patients (81.15%) fall in the pediatric age group under 18 years of age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This article summarizes the implementation of India’s first national rare disease registry and highlights key demographic and clinical trends. The NRROID provides foundational data to inform policy, research, and clinical care for rare disease patients in India.\u003c/p\u003e","manuscriptTitle":"Design, Development, and Implementation of India’s National Registry for Rare and Other Inherited Disorders","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-24 16:43:35","doi":"10.21203/rs.3.rs-6918670/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-11-13T02:43:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-12T19:35:57+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Orphanet Journal of Rare Diseases","date":"2025-06-18T17:27:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-18T13:28:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2025-06-17T23:34:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9322576f-1f40-4ecd-a34b-399f33918ce5","owner":[],"postedDate":"November 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T16:43:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-24 16:43:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6918670","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6918670","identity":"rs-6918670","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}