How collaboration changes the world for people with rare diseases

About 10 years ago, when Dr Gabriela Repetto was a resident in pediatrics at the University of Wisconsin–Madison, she received an email from the mother of two boys with intellectual disability, congenital anomalies and seizures. Gabriela and her team had recently diagnosed the two boys with a rare recessive condition. No causative gene was known at the time; Gabriela’s team had made the diagnosis through clinical findings only.

The email from the boys’ mother explained that, armed with the information about their diagnosis, she had found a few families with a similar diagnosis in other countries. She had also found a young researcher working to uncover the cause of the condition.

Within months, the causative gene was identified through collaborations between these families and researchers in nine countries across three continents.

Continued collaborations helped gather information to guide drug choice to treat the condition – a form of epilepsy – and there is ongoing research on animal models aimed at identifying therapeutic targets.

Rare diseases, by definition, affect a small number of individuals compared to the general population. In the United States, a disease is called rare if it affects fewer than 200,000 people at any given time. In Europe, the ratio is 1 affected person in 2,000. The total number of known, named rare diseases worldwide falls somewhere between 6,000 and 8,000 conditions. Although each individual disease is uncommon, their collective prevalence is estimated at 6 percent to 8 percent of the world population, implying that 450 million people have a rare disease. So in a sense, rare diseases are not as rare as they seem.

For people who suffer from them, and for their families, being diagnosed with a rare disease can be unsettling, so when doctors know how to proceed, it provides reassurance.

Most rare diseases are genetic in origin and are often tied to single affected gene. Given the genetic basis and varying symptoms, genetic testing is generally the most accurate way to go about diagnosis. But even with a diagnosis, treatments still have not been developed for the vast majority of these diseases.

Understanding and tackling rare disease requires a multi-pronged approach, pooling together knowledge acquired from various scientific disciplines, such as immunology, genetics, molecular medicine and pharmacology. When these disciplines come together, the results for patients can be life changing.

Dr Robert M Kliegman, Professor and Chair Emeritus in the Department of Pediatrics at Nelson Service for Undiagnosed and Rare Diseases, Children’s Wisconsin, has worked in pediatrics for about 50 years. He understands the tragedy of rare diseases – and the hope that comes through collaboration and progress:

I, along with my colleagues, have always been saddened when a child dies of some mysterious illness, sometimes acute but sometimes chronic, and there is no good answer for the family or medical team. With advances in diagnostic imaging and genetic sequencing, many of these mysteries are now able to be diagnosed and even treated. We have seen many families with children who were undiagnosed for many years finally have an answer and thus a better understanding of their child’s now diagnosed disease

Included among these articles is a paper co-authored by Dr Weida Tong, Director of the Division of Bioinformatics and Biostatistics at the National Center for Toxicological Research, US Food and Drug Administration, summarizing current standing and future possibilities offered by the clinical implementation of NGS-based genetic testing in rare disease.

About Rare Disease Day

The last day of February each year promotes awareness of rare diseases and the patients that suffer from them, as well as access to medical treatment and representation. Advocacy is critical for rare disease patients and their families. Whether it is improving disease understanding, connecting families with one another and with researchers, fundraising for research, or sharing resources, rare disease initiatives provide much needed support to patient communities. The National Organization of Rare Disorders, Perlara, the Rare Genomics Institute, the Iberoamerican Alliance for Rare Diseases, and Global Genes are just a few organizations that have provided meaningful outcomes for patients and families. Meanwhile, Orphanet and NIH – GARD (Genetic and Rare Diseases Information Center) gather and share information on thousands of rare diseases, along with other resources, to improve diagnosis, care, and treatment.

Access to worldwide promotion of this event can be found via #RareDiseaseDay.