India is home to an estimated 70 million people affected with rare diseases. Of these, 80% are genetic in origin. Many of these pass through a diagnostic odyssey and remain undiagnosed for 5-6 years, with the patient going from doctor to doctor. In recent years the advent of massively parallel sequencing, more of the disease patients are being diagnosed, and many are being provided treatment.
Recent estimates show that at least 21,400 children are born every year in India with Down’s syndrome and another 9,000 to 10,000 children with thalassemia. These diseases can be prevented by screening and prenatal diagnostic programs, but they have not been taken up in the national health programs in the country, and the patients pay out of pocket expenses to avail these facilities. A big awareness campaign needs to be carried out among the obstetricians while the Government should subsidize the cost of these tests. The total cost spent on the preventive program would be at least one -fourth the cost of looking after these affected children after they are born. In view of the shortage of clinical geneticists and genetic counselors in the country creation of network of centers will up scale the skills of doctors participating in the program and provide a cadre of well trained doctors to diagnose and treat patients with undiagnosed and rare disorders. This with the well developed biotechnology industry and good bioinformatic set up could result in the establishment of a highly successful program.
The message at the 7th International Conference on ‘Rare and Undiagnosed Diseases: Addressing Patient Needs in India’ was loud and clear — to make these relevant. The three-day event organised in Delhi in April by Undiagnosed Disease Network International (UDNI), Institute of Medical Genetics & Genomics at Sir Ganga Ram Hospital, Wilhelm Foundation, Organisation of Rare Diseases India (ORDI) and Institute of Genomics & Integrative Biology (IGIB) of CSIR called for the best and most effective collaborative efforts both nationally and internationally to share such experiences and find the way forward to solve and help patients with such conditions.
“In India, the scenario is more complex as the volume is enormous and it has many communities and different subgroups. Because we don’t have the frequency of variance of each of the subgroups, it becomes much more difficult to diagnose new diseases,” said William A Gahl from National Human Genome Research Institute at the NIH, US.
Dr Gahl, who is also the Director at NIH Undiagnosed Diseases Programme, added that most of the rare and undiagnosed diseases have got some or other link with the genetic base. “We have seen at the NIH itself about 1,200 to 1,250 patients and made some 320 diagnosis. We have discovered about 25 new diseases in the last ten years where a gene is associated with a particular phenotype of presentation.”
According to Dr I C Verma, advisor and key member of the scientific committee of the Conference, the main message of the 7th International Conference is that it is worth investigating the cause of rare and undiagnosed disorders, as this has been made easier by the application of massively parallel sequencing technology.
“Knowing the diagnosis, one proceeds to finding a treatment, which is the main concern of the patient and the family. Not knowing the diagnosis is very frustrating,” quipped Dr Verma.
“Contrary to usual thinking, rare and undiagnosed disorders affect a fairly large number of people in India,” added Verma, Advisor & Senior Consultant and Professor of Medical Genetics at Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, while talking to Future Medicine in a post-conference interview.
Attended by some 370 registered delegates, including practicing clinicians, students and researchers, the Conference was immensely rich in content with about 60 speakers from across the world sharing their case studies, experiments, ideas and vision.
“One of the key objectives of conferring here was to share and interact with colleagues and students working in the area of rare and undiagnosed diseases,” said Dr Ratna Dua Puri, organizing chairperson of the Conference, in an interview with Future Medicine.
She added: “With a lot of the latest sequencing facilities now available in the country and a fair number of clinical geneticists able to do deep phenotyping, we are able to help many patients. But, despite all these, there are still several cohorts with genetic disorders left undiagnosed. So, it is important to collaborate with colleagues and link the work done here as well as at other places and take the initiative as a community. This was the other main aim of this conference held in partnership with Undiagnosed Disease Network International.”
“A network of centers for undiagnosed diseases programs, with assessment by multi-disciplinary experts, exome sequencing, and bioinformatic analysis need to be set up in India” said Dr Puri.
This kind of conferences are also a wake-up call for countries like India, where genetic and metabolic disorders are usually diagnosed with poor outcomes.
“On this front, the major challenges in India at present include the small number of trained clinicians specialising in diagnosing and counselling genetic disorders, the few state-funded diagnostic and research laboratories, a lack of funding for genetic diagnostic tests and less accessibility for therapies and other interventions,” said Dr Meenakshi Bhat, Senior Consultant in Clinical Genetics at Centre for Human Genetics at Indira Gandhi Institute of Child Health, Bangalore.
According to Dr Seema Kapoor, in-charge of Genetics and Metabolism Division of Maulana Azad Medical College, New Delhi, though India has achieved significant milestones towards tracking genetic disorders through several government funded initiatives, including newborn screening for many congenital diseases since 2013, the challenges that still invite discussion are the feasibility of coverage in less developed areas, hilly terrains and home deliveries.
“Besides, the availability of good counsellors and a well-integrated follow-up system needs to be developed,” she said.
However, there is light at the end of the tunnel. Among others, one of the most recent collaborative research programmes—The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) initiated by the IGIB, has undertaken whole exome and genome sequencing for identification of variants and genes implicated in rare genetic diseases.
“Using Mitochondrial rare genetic disease examples, we will be able to share our experiences from the GUaRDIAN consortium where we apply genome sequencing followed by computational analysis and zebrafish disease modelling to solve several cases of undiagnosed diseases,” said Dr Sridhar Sivasubbu, Principal Scientist at CSIR-IGIB.
No doubt, only collaborative models will work in such a complex task of diagnosing unknown diseases to find treatments for them. Dr Gahl concludes that since the first meeting of the UDNI in Rome in 2014, there have been six international meetings, culminating in the 2019 conference in Delhi. In the past five years, over a dozen countries have established Undiagnosed Disease Programmes and the Network has created several common platforms to share experiences, information and views. The main focus of the Network involves sharing of genotypic and phenotypic data and best practices. And this, amongst others, can ultimately help advance the diagnosis and care of rare and undiagnosed diseases.