A rare disease is any disease that affects a small percentage of the population and most rare diseases are genetic and thus are present throughout the person’s entire life, even if symptoms do not immediately appear. Relatively common symptoms can hide underlying rare diseases leading to misdiagnosis and delaying treatment. Quintessentially disabling, the patients quality of life is affected by the lack or loss of autonomy due to the chronic, progressive, degenerative, and frequently life-threatening aspects of the disease. The fact that there are often no existing effective cures adds to the high level of pain and suffering endured by patients and their families. Rare disease is defined as a disease that affects fewer than 200,000 people across a broad range of possible disorders. Chronic genetic diseases are commonly classified as rare. Among numerous possibilities, rare diseases may result from bacterial or viral infections, allergies, chromosome disorders, degenerative and proliferative causes, affecting any body organ. Rare diseases may be chronic or incurable, although many short-term medical conditions are also rare diseases. Worldwide there are over 300 million people living with one or more of approximately 7,000 identified rare diseases, each supported by family, friends and a team of careers that make up the rare disease community. Each rare disease may only affect a handful of people, scattered around the world, but taken together the number of people directly affected is equivalent to the population of the world’s third largest country. Rare diseases affect 3.5% – 5.9% of the worldwide population. 72% of rare diseases are genetic whilst others are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative. 70% of those genetic rare diseases start in childhood. It has been found that many rare diseases appear early in life, and about 30% of children with rare diseases die before reaching their fifth birthday. With only three diagnosed patients in 27 years, ribose-5-phosphate isomerase deficiency is considered the rarest known genetic disease. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discovering treatments for it, except by the government granting economically advantageous conditions to creating and selling such treatments. Because of definitions that include reference to treatment availability, a lack of resources, and severity of the disease, the term orphan disease is used as a synonym for rare disease. But in the United States and the European Union, “orphan diseases” have a distinct legal meaning. The United States’ Orphan Drug Act includes both rare diseases and any non-rare diseases “for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will [be] recovered from sales in the United States of such drug” as orphan diseases. The European Organization for Rare Diseases (EURORDIS) also includes both rare diseases and neglected diseases into a larger category of “orphan diseases”. Orphan drugs are ones so created or sold. No single cut-off number has been agreed upon for which a disease is considered rare. A disease may be considered rare in one part of the world, or in a particular group of people, but still be common in another. In fact, there is no single, widely accepted definition for rare diseases. Some definitions rely solely on the number of people living with a disease, and other definitions include other factors, such as the existence of adequate treatments or the severity of the disease. In the United States, the Rare Diseases Act of 2002 defines rare disease strictly according to prevalence, specifically “any disease or condition that affects fewer than 200,000 people in the United States”, or about 1 in 1,500 people. This definition is essentially the same as that of the Orphan Drug Act of 1983, a federal law that was written to encourage research into rare diseases and possible cures. A disease defined as rare in Europe when it affects fewer than 1 in 2,000 people. In Japan, the legal definition of a rare disease is one that affects fewer than 50,000 patients in Japan, or about 1 in 2,500 people. However, the European Commission on Public Health defines rare diseases as “life-threatening or chronically debilitating diseases which are of such low prevalence that special combined efforts are needed to address them”. The term low prevalence is later defined as generally meaning fewer than 1 in 2,000 people. Diseases that are statistically rare, but not also life-threatening, chronically debilitating, or inadequately treated, are excluded from their definition.
The definitions used in the medical literature and by national health plans are similarly divided, with definitions ranging from 1/1,000 to 1/200,000. Prevalence (number of people living with a disease at a given moment), rather than incidence (number of new diagnoses in a given year), is used to describe the impact of rare diseases. The Global Genes Project estimates some 300 million people worldwide are affected by a rare disease. The European Organization for Rare Diseases (EURORDIS) estimates that as many as 5,000 to 7,000 distinct rare diseases exist, and as much as 6% to 8% of the population of the European Union is affected by one. Only about 400 rare diseases have therapies and about 80% have a genetic component according to Rare Genomics Institute. Rare diseases can vary in prevalence between populations, so a disease that is rare in some populations may be common in others. This is especially true of genetic diseases and infectious diseases. An example is cystic fibrosis, a genetic disease: it is rare in most parts of Asia but relatively common in Europe and in populations of European descent. In smaller communities, the founder effect can result in a disease that is very rare worldwide being prevalent within the smaller community. Many infectious diseases are prevalent in a given geographic area but rare everywhere else. Other diseases, such as many rare forms of cancer, have no apparent pattern of distribution but are simply rare. The classification of other conditions depends in part on the population being studied: All forms of cancer in children are generally considered rare, because so few children develop cancer, but the same cancer in adults may be more common. About 40 rare diseases have a far higher prevalence in Finland; these are known collectively as Finnish heritage disease. Similarly, there are rare genetic diseases among the Amish religious communities in the US and among ethnically Jewish people. The lack of scientific knowledge and quality information on the disease often results in a delay in diagnosis. Also the need for appropriate quality health care engenders inequalities and difficulties in access to treatment and care. This often results in heavy social and financial burdens on patients. Further, due to the broad diversity of disorders and relatively common symptoms which can hide underlying rare diseases, initial misdiagnosis is common. In addition, symptoms differ not only from disease to disease, but also from patient to patient suffering from the same disease. Due to the rarity and diversity of rare diseases, research needs to be international to ensure that experts, researchers and clinicians are connected, that clinical trials are multinational and that patients can benefit from the pooling of resources across borders. Initiatives such as the European Reference Networks (networks of centres of expertise and healthcare providers that facilitate cross-border research and healthcare), the International Rare Disease Research Consortium and the EU Framework Programme for Research and Innovation Horizon 2020 support international, connected research. If one is interested in looking for statistics on a specific disease, check if the disease is listed in Medline Plus Genetics or Gene Reviews. These resources usually include statistical information. To find medical journal articles with statistics, we can conduct a Pub Med search using the disease name and the word “prevalence” or “incidence.” There are many different causes of rare diseases. The majority are thought to be genetic, directly caused by changes in genes or chromosomes. In some cases, genetic changes that cause disease are passed from one generation to the next. In other cases, they occur randomly in a person who is the first in a family to be diagnosed. Many rare diseases, including infections, some rare cancers, and some autoimmune diseases, are not inherited. While researchers are learning more each year, the exact cause of many rare diseases is still unknown. Researchers have made progress in learning how to diagnose, treat, and even prevent a variety of rare diseases. However, there is still much to do because most rare diseases have no treatments. For many rare diseases, basic knowledge such as the cause of the disease, pathophysiology, natural course of the disease and epidemiological data is limited or not easily available. This significantly hampers the ability to both diagnose and treat these diseases. To address this challenge, public funding of fundamental research into the disease process remains necessary both at the national and global level. Rare disease patients are scattered across countries. As a result, medical expertise for each of these diseases is a scarce resource. A new generation of more targeted therapies (such as stem cell therapies, gene therapies or therapeutic gene modulations) is in development and new products are becoming available. To allow these targeted therapies for smaller patient groups to become more common practice, it is critical to continue funding the research and development of these highly innovative therapies. The National Institutes of Health (NIH) supports research to improve the health of people with rare diseases. Many of the 27 Institutes and Centers at the NIH fund medical research for rare diseases. One of these Centers, the National Center for Advancing Translational Sciences (NCATS), focuses on getting new cures and treatments to all patients more quickly. NCATS supports research through collaborative projects to study common themes and causes of related diseases. This approach aims to speed the development of treatments that will eventually serve both rare and common diseases. Efforts to improve and bring to market treatments for rare diseases are coordinated by the Food and Drug Administration (FDA). The Office of Orphan Products Development (OOPD) provides incentives for drug companies to develop treatments for rare diseases. Between 1973 and 1983, fewer than 10 treatments for rare diseases were approved. Since 1983, the OOPD program has helped develop and bring to market more than 400 drugs and biologic products for rare diseases. GARD website maintains a list of rare diseases and other terms to help people find reliable information. In recent decades, considerable attention has been paid worldwide to efforts to stimulate the research, development and marketing of medicinal products for rare diseases, including the use of various regulatory incentives. Rare Disease Day is observed on February 28, 2021. Rare Disease Day is an observance held on the last day of February to raise awareness for rare diseases and improve access to treatment and medical representation for individuals with rare diseases and their families. It was established in 2008 because, according to the European Organization for Rare Diseases (EURORDIS), treatment for many rare diseases is insufficient, as are the social networks to support individuals with rare diseases and their families. Rare Disease Day raises awareness for the 300 million people living with rare disease around the world and their families and carers. The long-term cause of the Rare Disease Day campaign is to achieve equitable access to diagnosis, treatment, health and social care and social opportunity for people affected by a rare disease. Important progress continues to be made with joint international advocacy efforts for universal health coverage (UHC), part the United Nation’s Sustainable Development Goals (SGDs) to advocate for equitable health systems that meet the needs of people affected by rare diseases in order to leave no one behind. Recently, rare diseases have received worldwide attention. The developing countries have fallen seriously behind in regards to awareness, drug development, diagnosis, and social services. India is to be considered as the “Pandora’s Box of genetic disorders.” Owing to its huge population heterogeneity and high inbreeding or endogamy rates, a higher burden of rare recessive genetic diseases is expected and supported by the literature findings that endogamy is highly detrimental to health as it enhances the degree of homozygosity of recessive alleles in the general population. The population of a low resource region Jammu and Kashmir (J&K), is highly inbred. Unfortunately, many suspected cases of genetic disorders remain undiagnosed or misdiagnosed due to lack of appropriate clinical as well as diagnostic resources in the region; causing patients to face a huge psycho-socio-economic crisis and many a time suffer life-long with their ailment. India, which has one-third of the world’s rare disease population, has neither accepted definition for Rare Disease nor an accurate assessment of the problem. Due to the exorbitant cost of orphan drugs, difficulties in diagnosis and treatments, the Indian government is often in a dilemma as to how to effectively, and efficiently formulate a National Health Policy for 1.3 billion people. India does not have definition for rare diseases and Government of India has no clear public policy on Rare Diseases or on Orphan Drugs. It is further compounded by lack of trained doctors or diagnostic labs etc. There are no incentives to Indian pharma industry to develop Orphan Drugs. This Day is the opportunity advocate for rare diseases as a human rights priority at local, national and international level as we work towards a more inclusive society. To conclude, the main objective of Rare Disease Day is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients’ lives. The campaign targets primarily the general public and also seeks to raise awareness amongst policy makers, public authorities, industry representatives, researchers, health professionals and anyone who has a genuine interest in rare diseases.
( While Dr. Syed Sabahat Ashraf is working at Regional Research Institute of Unani Medicine Naseem Bagh Campus Hazratbal Srinagar , Dr. Bilal A. Bhat is an Associate Professor at S K University Of Agriculture Sciences & Technology-SKUAST Shalimar Srinagar. Views are their own)