In this four-part series, we examine the various challenges faced by patients and families affected by rare diseases. We also interview clinicians, researchers, and the advocacy community at large to understand their perspectives on bottlenecks in rare disease diagnosis and treatment.
Part 3 of the series details some of the other challenges in the rare disease space: continued confusion and not knowing even after diagnosis, scattered rare disease communities, and getting the attention of governments to intervene.
“Mitchell was a normal kid with no real medical problems,” Michele Herndon said of her son during the early years of his childhood. “He had some asthma but that’s it. He played sports, was active, no concerns.”
At age 12, Mitchell began to complain of symptoms which marked the beginning of his rare disease journey. His legs started to “feel weird,” and he began to have balance issues. He also started having dry eyes.
“We took him to a neurologist who found spinal cord inflammation,” said Michele, who is also a pediatric nurse and Manager in Trauma Services & EMS Outreach at St. Louis Children’s Hospital. “This was the first big, concerning finding. At that point they came up with different diagnostic possibilities, but he didn’t really fit the clinical picture for them.”
Mitchell received some treatments but did not improve, only getting back to approximately 90% of his baseline by his 13th birthday, according to Michele. He then had a relapse at age 13.5 that put him in a wheelchair again. By the time a number of blood tests and biopsies started coming back as negative for known diseases, Mitchell’s doctors at Washington University started thinking about a rare, undiagnosed disease and suggested the family get second and third opinions. However, visits to neurology specialists at the University of Alabama and the Children’s Hospital of Philadelphia resulted in conflicting opinions of Mitchell’s diagnosis.
When Mitchell’s rheumatologist moved to Houston to work at Baylor College of Medicine, she contacted Michele and told her that Mitchell was a perfect patient for the Undiagnosed Disease Network (UDN) to study. Funded by the NIH and involving 12 US cities and their affiliated hospitals that function as clinical sites where medical experts and researchers can work together to make a diagnosis, UDN has received 3,392 applications to date and has accepted 1,311 participants.
“The Undiagnosed Disease Network is really for patients who have objective clinical findings and a unique presentation that, despite clinical evaluation, do not have a diagnosis,” geneticists at Washington University in St. Louis, a UDN site, said. “The patient has to be willing to undergo extensive clinical evaluations and it’s better if family members are available for genetic testing as well. Participants also have to agree to storage and sharing of information & biomaterials and can’t be too ill to travel safely to a study site.”
After receiving acceptance into the UDN program, the Herndons visited Houston, where Mitchell was evaluated by multiple specialists and had his genome sequenced. According to Michele, it was a good 6-9 months before they heard much back.
Confusion and the Challenge of Not Knowing
After a long wait, the Herndons finally started getting some answers.
“[Mitchell’s prior exome] had shown a mutation in ACOX1 but the physicians had always disregarded it because his disease didn’t match the known diseases for ACOX1,” Michele said. “But ultimately, they did decide that was what was causing his symptoms. They created fruit flies with his genetic mutation, which led them to this finding.”
With the help of the UDN, Mitchell was started on some new treatments that Michele says seems to be keeping him stable for the time being. However, she recalls how confusing the experience had been.
“It was all confusing, even for me as a pediatric nurse,” said Michele. “I thought that modern medicine could fix pretty much everything. It was such a surprise to me to find out that especially in neurology, there are a lot of times when they have to just say ‘We don’t know.’”
Geneticists at Washington University in St. Louis agreed.
“It’s no surprise that people are confused,” they said. “Everyone is confused by the changes and growth of what we know about the genome, how it works, and the technology we have to look at it. The field has changed so rapidly in such a short period of time that no one can keep up with it.”
Though Mitchell remains stable for now, he has been left with many deficits as a result of his rare disease. According to Michele, his most recent relapse has caused him to lose all movement and feeling from the chest down, including loss of bowel and bladder function. He also has some loss of hand function and is having to learn new skills. Despite having a diagnosis, Michele notes that not knowing the full prognosis is another challenge.
“I don’t think he’s going to gain back a lot of what he’s lost but if we can keep him from relapsing again that will be a huge thing,” Michele said. “[We have] no idea what the progression of the disease will be, no idea if the treatments he’s on will work, no idea if a small cold or new weird symptom is actually the beginning of a big decline and relapse. I think the major challenge is having no guidelines or community support.”
Scattered Communities, Isolation, and the Fight for Government Support
In addition to the challenges of an average diagnosis time of 5 to 7 years, limited FDA-approved therapies, and high cost of care, Ohio State Ambassador for NORD’s Rare Action Network Charlene York also believes that social isolation and small, scattered patient populations are additional obstacles faced by those with rare diseases. However, by becoming part of a rare disease advocacy group, York says patients and families can spark change.
“Patients and families affected by rare diseases can come together to use their voice,” York said. “At NORD we like to say, ‘Alone we are, together we are strong,’ meaning by coming together as one, we can help make an impact for all affected by rare diseases.”
Speaking of Ohio and other states like it, York notes that the creation of a formal, rare disease advisory council can provide an opportunity for stakeholders to make formal recommendations to the state on how to improve public policy for the rare disease community.
“In just the past 2 years, Rare Action Network has tracked and engaged in over 208 legislative bills with the successful passage of 31 bills and counting,” York said. “There is of course much more work to be done but there are many accomplishments that have impacted the rare disease community in a positive way.”
According to geneticists at Washington University in St. Louis, family organizations are informing researchers and medical professionals on how to best care for patients with rare diseases. But, they admit they can do a better job of empowering rare disease families to find the resources to band together and create the infrastructure to advance therapies and diagnostic tools.
“Parents and parents’ groups have been incredible advocates and have taught us a lot about what is really important as we do research and practice medicine in this space,” the geneticists said. “Families can use the internet or social media to find others like them and create a community. Sharing information between families who have similar experiences can provide a great deal of support. Some families have also formed organizations to fund scientific research into the disorder and have actually had some pretty remarkable success in that arena.”
Read Part 4 of the series here, which discusses the shortage of genetics specialists, limited medical knowledge, and the challenge of integrating extensive information.