Treatment for people afflicted with rare diseases is limited worldwide, especially in a developing country like India, where an underdeveloped basic public healthcare system already excludes a vast section of the population. Rare diseases are often serious, incapacitating, long-lasting, and potentially fatal. Children are particularly affected and roughly, 50% of these diseases manifest at birth.
Though the Union government released a National Policy for rare diseases in 2017, it was later shelved due to difficulties in implementation. State governments have voiced concerns over unclear provisions regarding cost-sharing, disease coverage, and patient eligibility for treatment. In 2018, a review committee was formed to tackle these concerns and it presented its recommendations in January 2021. Following further consultations, the revised National Policy on Rare Diseases (NPRD-2021) was unveiled in March 2021.
While this updated policy addresses some issues and provides directives, it still lacks a comprehensive structure to enhance the affordability and accessibility of treatment for the majority of patients.
What is a rare disease?
There is no universally accepted definition for rare diseases and typically, a condition that occurs with low frequency is categorised as rare. Various countries established their own criteria to address this, often considering factors such as the prevalence of the disease, the number of affected people, and the availability of treatments.
In the United States (US), rare diseases are defined as those affecting fewer than 200,000 people. In the European Union (EU), they are characterised as life-threatening or chronically debilitating conditions impacting more than 5 in 10,000 people. Japan identifies rare diseases as those with a prevalence of less than 50,000 or affecting one in 2,500 people, with no known cause or cure. South Korea sets the threshold at 20,000 and Australia at 2,000 affected people.
In China, a rare disorder is one that affects less than 1 in 500,000 people or has a neonatal morbidity rate of less than 1 in 100,000. In Russia, a disease is considered rare if it affects one patient per 10,000 people.
In Latin America, the criteria vary. In Brazil, a disease is classified as rare if it affects 65 or fewer people per 100,000, while in Colombia, the threshold is 2 per 10,000 persons. Argentina, Chile, Mexico, Panama, and Uruguay define a medical condition as rare if it impacts 5 out of every 10,000 people.
The World Health Organisation (WHO) suggests that a rare disease should be defined as one with a prevalence of less than 6.5-10 cases per 10,000 people, although some specialists contend that this cutoff is too high.
Drug development agencies have created their own definitions and eligibility requirements to receive regulatory and financial incentives for researching rare diseases and manufacturing treatments. These criteria vary because the overall conditions defining such diseases are not evenly spread across different geographical regions and are also influenced by factors such as genomic structure and social variables.
Certain diseases can have considerably different prevalence rates depending on the area and population. This diversity is especially visible in India, where research has shown that certain regions, such as Gujarat, Punjab, West Bengal, Odisha, and Andhra Pradesh, have higher rates of certain diseases like beta-thalassemia. Tamil Nadu has higher prevalence rates of rare diseases like Duchenne Muscular Dystrophy when compared to national averages.
India faces limitations in defining rare diseases due to a scarcity of epidemiological data. To overcome this challenge, the Indian Council of Medical Research (ICMR) has introduced a hospital-based National Registry for Rare Diseases, which currently includes only 12 specialised centers across the country. Notably, larger states have been excluded from this initiative. Consequently, the registry has made little progress in terms of data collection, reporting fewer than 500 cases of these disorders thus far.
V R Raman, the National Convener of the Public Health Resource Network (PHRN), emphasises, “Without having state-level registries and identification processes, it will be challenging for a vast country like India to identify such diseases. Over and above these we will have to also improve our disease surveillance data to capture the potential cases, so that a feedback loop could be built to prompt referrals and diagnosis.”
India is considered to be the Pandora's box of genetic disorders, Among the most frequently reported rare diseases in India are Thalassemia, Hemophilia, Sickle-cell Anemia, autoimmune disorders, Primary Immunodeficiency in children, Hirschsprung disease, Gaucher’s disease, Lysosomal storage disorders such as Pompe disease, Cystic Fibrosis, Hemangiomas, and certain types of muscular dystrophies.
In absence of accurate data, 70 million people in the country are estimated to suffer from such conditions. However, only 9,675 individuals have been registered in the National Registry for Rare and Other Inherited Disorders (NRROID), according to a response in Rajya Sabha in mid-2023.
However, the government's extensive data collection from carrying mothers, alongside the ongoing digitization initiatives, will expand the registry in time, maintains Dr S Suresh, who owns one of South Asia's leading private centers specialising in the antenatal diagnosis and foetal therapy.
Rare diseases diagnosis
Sujith Kumar, aged 37, a resident of Kerala’s Kannur, struggles with multiple skin conditions such as disseminated eczema, atopic dermatitis, oid oid, and seborrhoeic dermatitis. Expressing uncertainty about whether his conditions fall under the category of rare diseases, Sujith shares his frustration about undergoing various treatments, including Ayurveda, homeopathy, and allopathy, without finding a cure. He lost sight in one eye due to the side effects of the medication.
In the US, it can take up to seven or eight years for a patient to be diagnosed with a rare disease. In India, this journey is significantly prolonged due to the limited testing availability, restricted access to specialists, and inadequate understanding of these diseases, stemming from insufficient data. There are reports of challenges faced by families who are striving to have conditions like Infantile Hypophosphatasia and Niemann Pick Disease included in the policy.
As a consequence, patients experience a poor quality of life, and financial strain, and often remain undiagnosed. Traditional genetic testing involves only a handful of disease-specific tests. Usually, an accurate diagnosis is reached only after two to three misdiagnoses.
"I have a rare condition called Lamellar Ichthyosis. It was confirmed by a dermatologist at Thrissur Medical College, although I never underwent a skin biopsy to verify this condition," said 35-year-old Preethi Velayudhan, a resident of the Thrissur district of Kerala, who suffers from partial impairment of vision.
Preethi's mother, Satyabhama, who works as a daily wage laborer, took her to numerous hospitals across Kerala in search of a diagnosis and cure. However, they were unable to determine Preethi's condition for many years. Some medical professionals suggested it was psoriasis or leprosy. Others suggested the availability of treatments in Unani or Ayurveda. It took 29 years to finally identify the condition.
Further, families of patients are weighed down by financial burden as they have to resort to private healthcare facilities, given the lack of diagnostic services at government health centers, especially at the primary and secondary levels. 19-year-old Godwin, a resident of Ernakulam, Kerala, was diagnosed with Epidermolysis Bullosa and Ankle Ankylosis.
Despite being born in a government hospital with the condition, it was identified only at the age of 11 when he sought treatment at a private hospital. These delays in diagnosis highlight the lack of adequate healthcare services in the public healthcare system, particularly for identifying rare diseases.
Only 9,675 individuals have been registered in the National Registry for Rare and Other Inherited Disorders (NRROID), according to a response in Rajya Sabha in mid-2023.
Rare diseases are diagnosed only at specialised government health facilities located in urban regions, resulting in numerous cases going undiagnosed in rural India. Patients require clear guidance on which professionals to consult at each stage of diagnosis, referral to appropriate institutions, and subsequent treatment.
Additionally, a system should be established for healthcare workers to report screening and diagnostic data to tertiary hospitals, centers of excellence, and diagnostic centers. However, the existing policy lacks clear directives on coordinating efforts among different stakeholder institutions across various levels of healthcare.
Prevention and control of rare diseases
To prevent and control rare diseases, the policy promotes ultrasonography and biochemical screenings during pregnancy to encourage the prevention of birth in cases where rare diseases are identified in foetuses. Genetic compatibility testing for couples can also warn them against having children when they are identified as carriers with a high chance of conceiving a rare disease-affected foetus.
However, to achieve this goal, counseling and guidance centers need to be established at the district level to help people with rare diseases understand how to prevent and treat their condition. This requires extensive training of community workers like Accredited Social Health Activists (ASHAs) and providing specialist staff in local health centers.
But ASHAs haven't received the training to identify and inform the primary health centres about the rare diseases, said Surekha, the National Vice President of the ASHA Workers and Facilitators Federation of India, who is also the President of CITU Haryana State.
Government support in the treatment
Ravinder, an MGNREGA labuorer from Telangana’s Warangal, has two sons aged 16 and 14, both with severe lamellar ichthyosis. Ravinder recounts the ordeal faced by his elder son Avinash, who suffered from severe subvalvular stenosis, necessitating surgery at a private hospital. "After the surgery, we were on the verge of committing death by suicide because of the financial burden," he said, adding that there is no financial assistance from the government for people with rare diseases.
But the Panchayat authorities helped by issuing a disability certificate by “categorising them under mental retardation,” he shared.
The NPRD- 2021 categorises these diseases into three groups. The first can be treated with one-time curative measures. The second requires long-term or lifelong expensive treatments. Prohibitive is the third category whose cost might add up to crores.
Patients in the second and third categories, who need ongoing supportive therapies, often face challenges in accessing state funds. Even the upper middle class has to resort to crowdfunding for assistance.
Under the NPRD policy, the Union government initially intended to offer one-time financial aid up to Rs 20 lakh through the Rashtriya Arogya Nidhi scheme for the first category. This amount was eventually increased to Rs 50 lakh. However, there is still a lack of clarity on how the proposed benefits will be implemented.
The national policy recommends setting up a centralised crowdfunding platform specifically for patients in category 3 who require expensive and lifelong treatment. However, despite being in operation for years, this platform has had limited success in reaching and engaging donors. It has raised a meager amount of Rs. 2,93,797.
Even after diagnosis, the majority of rare diseases lack effective treatment options. Current research suggests that despite advancements in the field, only 5% of these diseases have a cure. However, for certain rare diseases without a cure, people can still achieve longer and improved lives through medication.
On December 27, 2023, the Times of India reported on six children diagnosed with a rare condition known as Gaucher disease. These children were undergoing expensive treatment at JKL Hospital in Jaipur, as mandated by the Rajasthan High Court. However, they have been deprived of medication for more than two months now.
At present, people rely on a few NGOs and foundations for assistance in covering the costs of treatment. Although assistance from foundations, NGOs, and crowdfunding initiatives is beneficial, it may not be accessible to everyone and provide only temporary relief. This highlights the necessity for continuous medical and financial backing for patients from the government.
Orphan drugs in India
Even for recognised rare conditions that have one or more standardised treatments, less than one in 10 patients worldwide receive precision treatments. While India has a higher rate of rare diseases than the global average, it still lacks national legislation for orphan drugs, which cannot be developed profitably by pharma companies without financial assistance from the government.
The government has started offering incentives for the manufacturers of orphan drugs and encourages private enterprises and start-ups to invest in developing diagnostics, medicines, and other products for rare diseases.
However, developing drugs for these diseases is complicated by several factors. These include not fully understanding the disease processes, a lack of standard drugs to compare new treatments to, limited scientific evidence, and no reliable preclinical models. Only some manufacturers produce Food for Special Medical Purposes (FSMP) for small molecule inborn errors of metabolism. The NPRD 2021 acknowledges that the high cost of most therapies prevents the government from providing them for free.
The government must procure them at a negotiated price from the private pharmaceutical producers, and make them available to the patients at an affordable price, Dr Suresh advocates. However, others are skeptical of the strategy of placing such reliance on private pharmaceutical companies for production, especially in the absence of profitable markets for such drugs.
“Leave aside orphan drugs, the private profiteers are not even going to undertake the large-scale production and supply of general drugs that give fewer profits. So the only way is to fund R&D as well as special grants to public sector drug manufacturers for small-scale production of the orphan drugs that are required for treating the rare conditions,” Raman insists.
“Over the last 3 decades, India neglected its public sector Pharma companies and we are going to pay the price. The sad part is that major struggles will be for the most neglected and marginalised people, and most persons with rare diseases would fall under this category. The US, Canada model of subsidising private pharma for production of these drugs may not work for the weaker and mixed health systems situation here,” he adds.
Despite some progress recently, there are still many challenges that make it hard for people to access and use these drugs. These challenges include identifying whether the drugs actually work and if they're worth the cost, high drug prices, problems with diagnosing these diseases, concerns about product safety, and a lack of knowledge and training. Like in the Global North, drug development and clinical trials are led by private players in India. But without a government-owned manufacturing system, these efforts are not sustainable.
Stigma associated with rare diseases
In India, rare diseases also pose a significant social challenge, as they are often associated with notions of bad luck and perceived as a curse from previous births. This stigma isolates victims of rare diseases, and families of the patients are often spurned by society.
Preethi’s father and his family abandoned her and her mother Satyabhama soon after she was born. Preethi recounted how during her time in school up to the ninth standard, she sat alone on a bench because other students were prohibited by their families from sitting with her. Children, unaware of the condition, used to call her cursed and spat on her mid-day meal. Despite her aspirations for further education, Preethi had to discontinue schooling after completing the tenth standard.
While taking the children to the hospital, Ravinder and his family were thrown out from the public buses by the other passengers who accused him of spreading infectious diseases. The extended families and neighbours barred him from using the water from the community handpump. Children and young people with rare diseases experience such negative social and psychosocial impacts, leading to lower self-esteem and resilience.
Nirmala, a 30-year-old woman living in Medchal, Telangana, faces the daily challenges of living with orthopedic disabilities and the rare skin disorder lamellar ichthyosis. Despite her resilience in coping with these conditions, her childhood trauma continues to cast a shadow over her life. Nirmala has received support from NGOs and health rights groups, aiding her in understanding and managing her conditions. Despite this support, her fear of dehumanisation and false pity made her reluctant to take a job that she was offered as housekeeping staff.
From the lack of clear definitions and diagnostic challenges to the financial burdens and social stigmatisation, the journey of those affected by rare diseases is fraught with obstacles. As we navigate these complexities, it is imperative for the government, healthcare authorities, civil society, and the public at large to come together in solidarity and action.
Anusha Paul is a freelance journalist and research associate with National Platform for the Rights of the Disabled. Her writing focuses on inclusive development and the advancement of disability rights.