Sarah Marshall knows first-hand how damaging a long diagnostic journey can be. Here, she explains how the Undiagnosed Diseases Network helped her family and how it helps to solve medical mysteries for others with nowhere else to turn

Written by Joe Rumney, RARE Revolution Magazine
An interview with Sarah Marshall, co-chair of the Undiagnosed Diseases Network

Sarah, can you give our readers an overview of the work of the UDN?

“The Undiagnosed Diseases Network (UDN) is a research study funded by the National Institutes of Health (NIH). It’s a network of clinicians and researchers, available (primarily) to anyone in the United States, which aims to uncover rare disease diagnoses and, hopefully, solve the most mysterious of medical mysteries for people left with nowhere else to turn.

“For many reasons, there’s usually very little collaboration between specialists, often because they work alone and there’s not enough time to consult. And the UDN is the answer to that—there’s a real collaborative effort towards finding a diagnosis for those desperately in need. In my eyes, the UDN is a national treasure.”

What was your own family’s diagnostic journey like?

“Phoebe, the youngest of my four children, started having symptoms at around six months old. At first, she came down with pneumonia, and then had several infections, and we constantly went between different doctors and specialists without any clear answers. Eventually, Phoebe was diagnosed and treated for myasthenia gravis [a rare long-term condition that causes muscle weakness], but as time passed, she noticed other unexplained and unrelated symptoms continued.

“In 2017, when Phoebe was eight, we entered her into the UDN study. We then travelled to Boston, Massachusetts, to have blood tests, and genomic sequencing was also done. As a result of the tests, the research team were able to identify the specific gene, called GDF11, which could have been the cause of her problems. And in a model organisms group, researchers found that when they changed that gene from a sample of flies and zebrafish, they experienced very similar symptoms to Phoebe’s own, which confirmed that the genetic mutation in the GDF11 gene was the cause of her condition.

“So, after a diagnostic odyssey of over a decade, Phoebe finally received a diagnosis at 13 years old, around four years after first entering the UDN study. Although four years may sound like a long time, without the UDN, she would still be without a diagnosis—and would likely still be suffering.

“With this new diagnosis, physicians could identify that the GDF11 gene, in part, regulates inflammation, and therefore prescribe the correct treatment. Now, as a 15-year-old, she takes her daily medication, self-administers anti-inflammatory injections, and has home- based, nurse-administered monthly infusions—these take almost an entire day. Aside from that, Phoebe lives as any typical teenager would.”

What difference has the diagnosis made to your lives?

“During that long diagnostic odyssey, Phoebe missed around 60 days of school each year because of hospital stays, medical appointments, surgeries and bouts of illness. After she received that second diagnosis, however, her attendance drastically improved; she missed out on only 20 days each year. That’s extremely important, not only for her education, but also because she wasn’t having much social interaction with her peers. That unknown illness took so much of her childhood away.

“At the same time, trying to find a diagnosis seemed impossible—no doctor could give us any answers. Some would say they knew something was wrong with Phoebe, while others would insist that nothing was wrong with her. In my opinion, when these doctors had no answers, their default was to turn it back onto us, the family, and pretend it was all in our heads. As a parent, I had to balance managing the relationships with the providers to keep them on-board and not offend them, because we needed them to help us find the answers. That was probably one of my biggest stressors during that time.”

What changes are you currently advocating for and why?

“I’ve volunteered with the UDN Participant Engagement and Empowerment Resource (PEER) patient advocacy group since 2018, and I’ve also recently become their co-chair. And lately, we’ve been working on the sustainability, trying to ensure the longevity of the UDN. As it’s funded through a common fund, which only lasted for ten years, we wanted to ensure the National Institutes of Health (NIH) continues funding beyond that, along with other sources of funding, because I believe the UDN is an essential service for families like mine.

“We had many meetings with different legislators around the country. In the end, Congress agreed to allocate $18 million to continue the funding. So we’re now working to make sure that funding remains each year. Currently, there are 14 UDN sites in 12 cities around the United States, and we aim to expand those services to give those underserved populations in rural areas better access. I think everyone in this industry has the same goal: to help people find their diagnosis, so that everyone has access to both diagnosis and treatment, because without a diagnosis there is no treatment.”

What is the value of newborn screening in reducing the burden of disease for families?

“There is a large undiagnosed population around the world, so newborn screening can remove the diagnostic odyssey, which takes on average, seven years, and help people to treatments if they are available. For many rare diseases, severe disability or even death can happen without immediate treatment, so early diagnosis helps prevent that.

“People wonder why a diagnosis is so important, but if you don’t fit into a ‘diagnosis box’, physicians are very hesitant to treat you.”

“Newborn screening serves everyone, but I think, in particular, it can serve rural populations, who could live hours away from facilities and specialists. I know first-hand the stress being undiagnosed puts on families. If their child gets sick and isn’t eating, where do they go for help? Newborn screening can let them know soon after the tests, and they can get access to the treatments they need.

“Two years before Phoebe had her initial diagnosis of myasthenia gravis, she complained about what I now recognise as weakness—she couldn’t even squeeze a tube of toothpaste. So we visited countless doctors, but nobody could ever explain why she was feeling this way. It got to the point where she would cry because she felt so exhausted, and she often didn’t want to leave the house. We felt hopeless for a long time. But now she has treatment, she’s able to more fully participate in normal life. Getting that diagnosis really does lead to a better quality of life.”

Editor’s note: To find out more about the work of the UDN, please visit: undiagnosed.hms.harvard.edu

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