Skip to main content

Unfortunately we don't fully support your browser. If you have the option to, please upgrade to a newer version or use Mozilla Firefox, Microsoft Edge, Google Chrome, or Safari 14 or newer. If you are unable to, and need support, please send us your feedback.

We'd appreciate your feedback on this new experience.Tell us what you think(opens in new tab/window)

Publish with us
ELS Editorial rare diseases illustration

How collaboration changes the world for people with rare diseases

February 25, 2021

By Peter Linsley, Kerry Holland

In recognition of #RareDiseaseDay, Elsevier is making select research articles and book chapters freely available for two months

About 10 years ago, when Dr Gabriela Repetto(opens in new tab/window) 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.

Gabriela, who is now Professor of Genetics at Facultad de Medicina Clinica Alemana, Universidad del Desarrollo in Santiago, Chile, recalls the impact these developments had on her:

Although I had participated in international collaborative projects before, I still remember this as a powerful experience of the momentum generated by that email, and the results of the strong connections between families, clinicians and researchers globally.

Gabriela is one of dozens of authors whose work Elsevier is making freely available for 60 days, beginning on Rare Disease Day(opens in new tab/window) (#RareDiseaseDay(opens in new tab/window)) February 28, 2021. Content includes Clinics(opens in new tab/window) review articles, book(opens in new tab/window) chapters, and articles in the Cell Press (opens in new tab/window) portfolio, all intended to support researchers and clinicians in identifying the molecular basis of these diseases, advancing drug discovery and drug repurposing efforts, translating findings to the clinic, and counseling patients and families. Leading articles from Elsevier’s Clinics and books detail a range of specific diseases, from rare congenital malformations to neurological disorders.

Image of Prof Gabriela Repetto

Prof Gabriela Repetto, MD

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(opens in new tab/window). In Europe, the ratio is 1 affected person in 2,000(opens in new tab/window). 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(opens in new tab/window). 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.

Dr Michael Frumovitz(opens in new tab/window), Professor of Gynecologic Oncology and Associate Chief Patient Experience Officer at the MD Anderson Center(opens in new tab/window) in Texas also has work featured in the collection. He highlighted the difference sharing knowledge can make, not just in a practical sense but in terms of the impact it can have on sufferers. He explained:

I have had multiple patients tell me their doctor had said to them, ‘I have never seen a patient with this type of cancer before. I’m not sure what to do.’ This can be incredibly discouraging, disappointing and scary for patients. When we tell them we have substantial experience in treating women with their rare cancer, the relief in their face is immediately clear. We hope we can share our expertise with providers so that they can say to their patients, 'I may not have seen this before, but I know what to do.’

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.

Michael Frumovitz

Michael Frumovitz, MD, MPH, FACOG

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(opens in new tab/window), Professor and Chair Emeritus in the Department of Pediatrics at Nelson Service for Undiagnosed and Rare Diseases, Children’s Wisconsin(opens in new tab/window), 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(opens in new tab/window), Director of the Division of Bioinformatics and Biostatistics at the National Center for Toxicological Research, US Food and Drug Administration(opens in new tab/window), summarizing current standing and future possibilities offered by the clinical implementation of NGS-based genetic testing in rare disease.

Dr Tong explained why this was so critical and how it can make a different to sufferers and their families:

The average length of accurate diagnosis of a rare disease is 4.8 years and involves more than seven physicians or specialists who may be geographically distributed. The genetic diagnosis may not be directly associated with any treatment options, and physicians will continue to treat symptoms, albeit in a more informed way based on likely prognosis of the case. Therefore, genetic diagnosis could be of benefit beyond treatment management as it can offer information to families, many who just want to know what is wrong with their family member and can also inform fertility decisions.

Please see the links below(opens in new tab/window) to freely access this content through April 30, 2021.

Weida Tong

Weida Tong, PhD

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(opens in new tab/window). 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(opens in new tab/window)Perlara(opens in new tab/window), the Rare Genomics Institute(opens in new tab/window), the Iberoamerican Alliance for Rare Diseases(opens in new tab/window), and Global Genes(opens in new tab/window) are just a few organizations that have provided meaningful outcomes for patients and families. Meanwhile, Orphanet(opens in new tab/window) and NIH – GARD(opens in new tab/window) (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.

Free access to research on rare diseases

This content is freely available through April 30, 2021:

Book Chapters

Clinics articles

Articles in the Cell Press Trends portfolio