Many people living with a rare and undiagnosed disease face a prolonged diagnostic odyssey that can be financially and emotionally taxing as they seek to put a name to what ails them. Co-founder and executive director of the Rare and Undiagnosed Network Gina Szajnuk and Co-founder and acting executive director of the Undiagnosed Diseases Network Foundation Cristina Might, both know what the search for a diagnosis is like and are working to help people find answers faster. Ahead of Undiagnosed Rare Disease Day April 29, we spoke to Szajnuk and Might about their own diagnostic odysseys, efforts to speed the path to a diagnosis, and the upcoming Undiagnosed Rare Disease Day.

 

Daniel Levine: Gina, Cristina. Thanks for joining us.

Gina Szajnuk: Thanks for having us, Danny.

Cristina Might: Absolutely.

Daniel Levine: We’re going to talk about living with an undiagnosed rare disease, our changing ability to diagnose patients with unrecognized rare conditions and the upcoming Undiagnosed Disease Day. Both of you, I suspect will be familiar to our listeners, but I I’d like to start by having each of you talk a little about your own stories and lives, and living with an undiagnosed rare disease. Gina, you and your children have undiagnosed diseases. When did the diagnostic odyssey begin for you and your kids?

Gina Szajnuk: Well, it really started when I had Ava, my oldest. So, I Ava is 14, now Oscar is 12, and Lucy’s 10, and I had a C-section with Ava and my body just came out on fire and everything just kind of changed after that, but I didn’t really think about it. You know, you’re a new mom. You just want to move on and focus on your baby. I ended up going through three more pregnancies, all C-sections and just put my health on the back burner. And then we realized when Ava was about five—well, when she was three, she was diagnosed with an arachnoid cyst, and a lot of people live their whole lives with an arachnoid cyst, but it changed our thought process on raising her—no soccer, no water skiing, no skiing. It’s just—never to hit her head. So that kind of changed, you know, being a mom and not everything’s healthy, and perfect is what you thought your journey was. But I say a lot of times, I wish I could go back to when Ava just had an arachnoid cyst. So, she started having these very bizarre symptoms, redness in her hands and fatigue and when she was five and that is kind of when the real diagnostic odyssey began. At the time we were living in New Jersey and then we moved to Chicago and we were at all the hospitals in Chicago, a little bit in Wisconsin and a neurologist—we went through every department with her. I think we started in dermatology, to rheumatology, and then every specialty, but ended in neurology. And I will never forget when the neurologist sat towards me, her elbows on her knees, and just took a big breath and just said, Gina, you will never have a diagnosis for Ava. She’s undiagnosed and we will treat her symptoms. That put a spark in me to say absolutely not, and that’s truly when the official huge diagnostic odyssey began, because I wasn’t going to accept that at the time. And then we went on the journey to Mayo clinic to about nine to 10 institutions and she’s 14 now, so it’s been a long journey. Then you add in Oscar and Lucy, we realized quickly after that, that Oscar had it, then we realized Lucy had it. And then we came back to visit my health. At the same time, we were all getting worked up in about 2012, 2013.

Daniel Levine: Is the assumption that all four of you share a condition.

Gina Szajnuk: We like to say, we have a constellation of symptoms. We’re not all the same because Ava’s had the four cranial surgeries from her subdural hygroma where none of us have had that. So, it’s very interesting, but the general umbrella “undiagnosed disease pattern,” which we say is an undiagnosed autonomic neuropathy, an undiagnosed genetic dysfunction, is the same for all four of us.

Daniel Levine: I think we start to get numb just hearing the statistics of undiagnosed rare disease and the average time it takes to get a diagnosis and how many doctors someone sees, but give us some sense of what it’s been like to live through that. How difficult has it been to get doctors to take you seriously, get access to appropriate diagnostic tests, and getting care when needed.

Gina Szajnuk: For our family? We’ve been very blessed. I think in the beginning it was hard to be taken seriously. I remember even with her arachnoid cyst, the pediatrician just said, “it’s just the way her skull was formed.” And I begged him to refer me to a neurologist neurosurgeon because she had this large skull bump on the left side. And he finally said to me, “I’m going to humor myself and send you to the neurosurgeon and I can’t wait to see him say, it’s, it’s nothing it’s benign.” Well, it wasn’t, it was an arachnoid cyst and that ended up having to have a cyst administration. She had two external drains. She had cyst administration. She’s now shunt dependent. And if you go back to that moment, it’s devastating to a mother. When your gut tells you there’s something wrong, and especially after she did hit her head in May 2013, we couldn’t get anybody to believe us or understand, and she would scream like a wild animal at night and sure enough, it took her to start going blind with papilledema in the ER at the Children’s Hospital, Wisconsin, before they did listen. They were going to send us home on Thursday to come back the next Tuesday for a neuro consult. In that time, she definitely would’ve been blind and most likely passed away. So, I think that urgency in the mother is to listen to that gut feeling always. But I think since then, our journey’s been wonderful even at Children’s Hospital, Wisconsin. They had a whole team, which I think is interesting, a secret medical team that’s watching everything going on in the hospital. And they were assessing our situation. They were getting the medical records from Mayo Clinic and after her shunt surgery, we went on that undiagnosed autonomic neuropathy path with them, with Mayo. Then we moved to Utah and our team here at Utah was fantastic. So, we’ve been blessed in that. I think because we have the documentation from the trauma that helped us move our path forward. I also have very visual distal joints that show that there’s something wrong with me, even though you can’t tell from any of the four of us that were ill because it’s invisible. But I think bringing into our conversation and why Cristina Might is part of our journey is that we also then applied to the Undiagnosed Disease Network, the UDN, and were accepted as the first family to be accepted back in 2015-16. And then you’re in that world and it’s a wonderful world to be able to be accepted to. And that was a journey through the UDN that we went through.

Daniel Levine: How does not having a diagnosis, complicate getting insurers to pay for what you need.

Gina Szajnuk: It definitely complicates it. It’s a lot more peer to peer calls for doctors. I think there’s scans. I remember an important scan that we never did get approved. And I think we fought for it for about two to three years, a PET scan. It’s hard because at the time whole genome sequencing wasn’t approved and then luckily we were with the Youth to Genome project. So we went through the research side of things. So, I think it is really hard. It’s very time consuming. Exhausting. You’ll get your hopes up to have an exam or a test ordered, all the fun, then to get the piece of paper in the mail saying it will not be approved.

Daniel Levine: Cristina. I think many people in the rare disease community felt a gut punch when they learned that your son Bertrand had died. He became the first person diagnosed with NGLY1 deficiency, a genetic neurodegenerative condition. What did it take to get that diagnosis for?

Cristina Might: My goodness, Danny, this really takes me back, and listening to Gina. I think I have a little bit of PTSD when it comes to the diagnostic odyssey, especially when looking back on Buddy’s journey. I’m really struck by how fortunate he was, how fortunate we all were because his diagnostic odyssey only took four years. He was very fortunate to be one of the first patients in the world to have access to clinical exome sequencing and you know, to have a mother who could take him to Cleveland Clinic, Johns Hopkins, NIH, Duke, and other places just like Gina. And I feel struck by the amount of privilege that have. We’re college educated and we had the resources to be able to travel, the ability to be able to go without having to work and do all of these things. And the thing is undiagnosed diseases are limited to people with means. There are so many other patients and their families who don’t have those things, also struggle. But you know, I would love to hear more from them and figure out what we could do for them. But Bertrand’s journey was long. It was arduous. Like Gina, he almost died multiple times. We spent as long as six weeks in the ICU at any given point, every kind of testing known to man and was done on that poor baby. And you know, I miss him every day, but I think that that just underscores why Gina and I, and so many others within the UDN and the global undiagnosed disease community, like my colleague, Colleen Sederach from Sweden and many, many others are working together to try to come up with a better solution for the undiagnosed and for the newly diagnosed.

Daniel Levine: When you did get the diagnosis, even though this was a newly discovered disorder, how did having a name for it and knowing what it was, change things for you?

Cristina Might: Well, it changed things a lot and then it didn’t change things at all. Okay. If that makes any sense, having a name to a disorder and we actually got to name the disorder, was very empowering. It made us feel like we were less crazy. It gave, felt, made us feel validated with doctors and scientists, but also with family members and friends, gave us the ability to pursue family planning options and have more children. It gave us the ability to pursue therapeutics and other critically vital things. But by the same token, it just launched us on a totally new odyssey, which was that of therapeutic development. When no community exists, when no pre-existing science or therapies exist, you’ve just left one island and moved on to another. So, it was great, but at the same time, it kind of kind of left us still very much feeling adrift.

Daniel Levine: I think people who are caregivers can often neglect their own health needs. You’ve had your own rare disease. You were diagnosed with myasthenia gravis, a rare autoimmune condition that is relatively well understood, but how long did it take you to get diagnosed and how quick were you to pursue a diagnosis?

Cristina Might: Oh, my goodness. This is almost embarrassing. I’ve been diagnosed with generalized myasthenia gravis and it was in part because do as I say, not as I do, right, you’re supposed to engage in self-care. Everybody tells the caregivers. Yes, of course, sleep, eat, do the things you need to, but when your child is ill or your loved one is ill, you don’t really take time to do those things. It took me, I want to say, close to two years to get diagnosed for a very well-known rare disease, one that we have a great deal of support for, because even though I am a very strong advocate for my child, I am not necessarily the strongest advocate for myself. And those were two totally different challenges that I faced. I’m trying to get better at self-advocacy right now, so hats off to those who’ve been on this journey much longer than I have.

Daniel Levine: It’s interesting because we talk about the diagnostic odyssey all the time, but you’ve actually encountered what you’ve referred to as a therapeutic odyssey. I’m wondering if you can explain that.

Cristina Might: Yes. I think that a lot more people undertake a therapeutic odyssey and honestly a diagnostic odyssey, when I look more broadly at conditions—once upon a time, things like autism or cerebral palsy or epilepsy, these common ‘quote unquote’ conditions that we’ve since found to be more rare conditions, we just group based on phenotype. I see things like depression, anxiety, ADHD, and these other common conditions. And I feel like the future of medicine is really trying to phenotype those and understand those conditions so that they can be more quickly and accurately treated, same as rare disease. So hopefully we can do a better job of accurately diagnosing patients, no matter what, to accurately treat them. And this odyssey is—it’s crippling, it’s very time consuming even in the cases where there is an existing treatment, like in myasthenia gravis, I’ve already gone through several treatments. It’s very dependent on the individual. It’s very personalized. And now science has, I think, outpaced medicines, administrative, or bureaucratic or other capabilities. I think it’s a great opportunity for the rare disease community, but also for medicine more broadly because we do have a lot of great understanding that exists almost in silos. And now there’s an opportunity for the patient community to come together and encourage all stakeholders to play a role in this and to start bringing those pieces together, to have communication, collaboration, and to share so that we can hopefully optimize and accelerate the rate at which you get diagnosed and treated because that odyssey is very isolating, no matter which leg of it you’re on.

Daniel Levine: Both of you are involved in important work for people with undiagnosed rare diseases. You’re co-founder and acting director of the Undiagnosed Disease Network Foundation. What is the Undiagnosed Disease Network Foundation and what is it working to do?

Cristina Might: We call it the UDNF for short, but the Undiagnosed Disease Network Foundation is a new global patient organization representing the interests of the undiagnosed, the misdiagnosed, and the newly diagnosed patients and their families who want to see clinical action for patients today, not waiting for some distance future, so really trying to serve as that bridge builder between academics, clinicians, researchers, industry, policy makers, and other patient groups and organizations to get everybody to work together. One of the vehicles that we’re using is the Undiagnosed Disease Network, which was a program of the U.S. government’s NIH Common Fund. And that network was incredibly successful in discovering, phenotyping, and starting next steps for brand new rare diseases. Patients such as Gina were a part, but there’s still many patients who remain undiagnosed. And then there’s that issue of that next step. It’s not particularly fair to expect patients and their families to drop everything, quit jobs, start foundations, and just become therapeutic development experts. So, using that infrastructure that Uncle Sam paid for that is the UDN to hopefully build out a shared infrastructure for therapeutic development, as well as improving diagnosis more broadly and in more than just genetics, because as Gina can tell you, there’s some epigenetic factors, possibly environmental exposures, other things that come into play when it comes to rare undiagnosed diseases. We need to start building those tools. They can be diagnostic tools, clinical tools, but also informatic tools, artificial intelligence, machine learning, all of these natural language tools that are coming about and really trying to knit all those pieces together so they’re not just existing in academic silos, and hopefully start creating some real action because the terrifying part, and I’m sorry if I’m running on, is that in 10 years from my son’s diagnosis, I would’ve thought that the state of affairs would’ve been different for new people and new patients and families being diagnosed today and tragically they weren’t, they were still having to shoulder that burden almost single handedly. There didn’t exist, and there doesn’t exist that shared infrastructure yet—so transforming the UDN into what patients and families want and need is really the goal of the UDNF.

Daniel Levine: The UDNF is coming at a time when the UDN is about to lose a significant portion of funding. Can you explain that?

Cristina Might: Yes. So, the UDN was a program of the NIH Common Fund. By law, those fund programs can only go on for 10 years so this is the end of the 10th year coming up and it is known and widely touted to be the gem of the NIH Common Fund. It was the most successful program in NIH Common Fund history. It has done phenomenal things, but their hands are basically somewhat tied when it comes to what they can and can’t fund. So, we’re trying to find new, innovative ways to partner or to create new programs, to extend the capabilities of the network, which is what patients and families want anyway, and hopefully really evolve it and expand it to reach more patients within their communities to hopefully expand things globally. And we’re trying to merge what’s known as the Undiagnosed Diseases Network International and the UDN together, patients and families being that glue that binds them to serve not just all the families here in the U.S. Rare doesn’t care about geography. There are patients in the third world or in developing countries that deserve diagnosis and treat just as much as my child did. So, we can’t turn a blind eye to them, especially when some of the conditions that they face are even more devastating. We’ve, Gina and I, never were under the threat of being stoned to death for saying that our child had a rare disease or being cast out of family, our community because we were seen as having demonic possession or witchcraft for having an undiagnosed rare disease. Giving these patients a name there, like you said, doesn’t just give them all the options and benefits that I mentioned. It also gives them their humanity back, which as a mom, as a rare disease patient, as a human being, I feel an ethical and moral obligation to try our best to make that possible.

Daniel Levine: You say you were never stoned, but I was kind of astounded to learn of the online harassment you suffered in seeking to find answers for your son.

Cristina Might: Oh, yes. That was early on before data sharing became commonplace, and we had very limited options with how to find other patients or researchers or resources to help Bertrand. This was in the dawn of the internet era. This is back in 2010, 2011, 2012. Our family’s story went viral. This was back when viral had just kind of become a term and internet trolls were alive and well. But even within our own community, even responding to newspaper stories, et cetera, people were incredibly cruel, saying that we should be sterilized, that my son should be put down, that he should be suffocated, I should take a pillow and smother him, that we were irresponsible, that people like us shouldn’t be allowed to breed. The vitriol was intense. And I don’t think that, on top of dealing with a sick child, any parent should have to deal with that or any patient themselves, but that’s what you find out there. And that’s the other side of being so open and advocating and sharing your story. And that’s something that nobody warned us about because it was early days, but anybody who has shared their stories probably now maybe expects some of the internet trolls to come out of the woodwork, but back then I was totally unprepared for the hate.

Daniel Levine: You mentioned, by law, the funding that UDN has received through the Common Fund is going to be going away. How much of a gap does that leave?

Cristina Might: Well, thanks to patient advocacy and the patients and families of the UDN, as well as the great people who work at the NIH, they’ve chosen to expand, or create a program to help fund a coordinating center for the UDN at $5 million per year, for five years. That leaves a funding gap of $15 million a year. The brunt of that goes to the sites that are in the trenches that are covering some of the cost for patients who don’t have Medicaid or the patients who do have Medicaid, but can’t travel out of state. And so the UDN currently covers all of that. So, the ones who are unfortunately bearing the cost of that are like the least of our community, the most underserved, which is absolutely tragic. And I think that’s the intent, but they need to hear from us. They need to hear from patients and families, they need to hear from the broader rare and undiagnosed community—anybody’s ever been undiagnosed probably should speak up and let Washington know, let others at the NIH and elsewhere know that this UDN program should be preserved in some way. It would be wasteful. It’s been an incredible investment, one of the best investments that the U.S. government has put together. So, I would love to see it continue, but I’m very biased.

Daniel Levine: Gina, you’re the co-founder and executive director of the Rare and Undiagnosed Network. What is RUN and what does it do?

Gina Szajnuk: Well, RUN came out of our experience with Ava in our journey. I felt alone at the time, so I created, with Dr. Reed Robinson back in 2014, the Rare and Undiagnosed Network to get our story out there, but also to build a network of researchers, physicians, patients, advocacy groups, and bring everybody to one platform to share not only our journey, but anybody’s journey that’s been on this diagnostic odyssey, and just to make a community for not only the mothers, but also the children. I was worried about my children going through school, high school, college life, thinking they were alone. And Through RUN, it took its own life and became something bigger than our family. And now my children do have a community. I have a community, and it brought a lot of opportunities, Christina has talked about this because I’m also helping with UDNF in any way that I can, but I think RUN really focused on education advocacy. In the next few years, I really want RUN to focus on action. And so what Christina is doing with the UDNF and through the UDN and the UDNI—that’s helping to also bring actionable causes our way to also support them, and every way that we can support the undiagnosed community. So I feel like RUN evolved from advocacy and educational experiences to how can we be actionable for the community.

Daniel Levine: As the two of you think about people who are suspected of having a rare genetic disease that’s undiagnosed, do you think we’re better at finding answers today? Is there something that gives you hope that we’re going to be able to find answers faster for more people?

Cristina Might: I feel like we are finding answers. I know we are finding answers faster for a lot of conditions now, but it’s leaving behind a lot of the ones that are the hard cases. I think especially at academic medical centers, those that are un diagnosed there tend to be difficult cases to diagnose. And I think there’s going to be multi-genomic or multi-factor conditions, like we said, epigenetic conditions or maybe environmental factors, others that are complicating a diagnosis. We’re now going to have to start expanding the field of genomics and of diagnosis to be able to find answers for these patients. But I think in other communities and in other places, all it would take would be running the right test or getting that covered. So we really do need not just the science to be there, but we also need the advocacy. We need the policy, we need the education, the awareness, all of those community and other factors need to be there too. We can’t just do science. Although the science is critically important, we need all those other pieces to be aligned. What do you think, Gina?

Gina Szajnuk: I agree with that. Back in the day when Ava was 5, 6, 7, they said it’ll be 20 to 25 years before science catches up to be able to help us. She’s 14 and it just feels still far away for the complicated, disease processes that unfortunately our family falls into, but I have hope with a lot of things, like Christina’s talking about, it’s not just the science, it is everything. And that’s why we’re still sharing our stories now and continuing on this diagnostic odyssey to just to keep push pushing forward in everything that Christina mentioned, science policy, everything.

Daniel Levine: Both of you are going to be working with the data sharing platform, RARE-X to encourage people who are undiagnosed to share their health data. Why does this matter?

Cristina Might: Well, I think community is so much more when it comes to undiagnosed than people give it credit for. I think there’s power in numbers, having a better idea of the scope of the undiagnosed problem, being able to use that kind of data to maybe facilitate matching across not just states, but geography across the world to be able to identify more patients like you, even if they haven’t been able to identify anything within your genetic testing, be it through matching with different phenotypes and then they can look and find matching there for community. Also, the issue of the undiagnosed has not fully been understood. I think there’s so many other people who probably feel misdiagnosed as well, so being able to really capture that and present it and share it in such a way that it is collaborative and that it can just interface well with industry so when patients want to go to FDA, so when patients want to develop therapeutics, when they want to pursue getting treatments approved, the data is already there. They’re not having to go back through and recreate the wheel. They’re not having to, “Oh, I filled out this patient registry, well now have to create another patient registry for therapeutics”. No, this way you’re only doing everything once instead of having to fill out form after form after form, time, after time, after time. Hopefully this will be a big time saver for patients and families, but also for clinicians, researchers, and companies who are interested in hopefully solving problems for these patients and families.

Gina Szajnuk: For me, what it gives me and our family and all the families that are undiagnosed or even rare is just to have that collaboration and not feel like you’re at a dead end and not to be that word we use over and over again—siloed. I feel like it’s opening this whole new world to these patients and people and families that there’s going to be this world of collaboration. And that gives me hope, a lot of hope.

Daniel Levine: Most of our listeners will be familiar with Rare Disease Day, which takes place at the end of February. The end of April marks Rare Undiagnosed Disease Day. Gina, how will you be celebrating this? And what is the goal of Rare Undiagnosed Disease Day?

Gina Szajnuk: I think the goal of Undiagnosed Rare Disease Day, or short Undiagnosed Day, is just to raise awareness, obviously within our community, but with the general public as well and to really shine a light on the severity of the international problem with the undiagnosed rare disease community, and to also celebrate everyone that’s involved in the undiagnosed rare disease community, as you know, the physicians, everyone that’s working in this space—researchers and industry and policy makers—to just say celebration, but also to keep pushing forward and to have our voices heard and to just be as loud as we can and just to get the attention of the general public and to celebrate and raise awareness for undiagnosed rare disease families.

Daniel Levine: For people who would like to participate in Rare Undiagnosed Disease Day, what can they do and where can they go to find out more?

Gina Szajnuk: I think we’re going to have a lot on social media, there will be a lot of things that’ll be put out there before Rare Undiagnosed Disease Day. With COVID still, we haven’t really done any live events locally or nationally this year, but hopefully next year we’ll be able to get back to in-person events.

Daniel Levine: Is there more information that they can find on the RUN website?

Gina Szajnuk: Yes. I will be putting out more information on the day and leading up to the day. At rare undiagnosed.org, they’ll be a lot of information of how to share the information that we have on our site. We also have Ava’s ribbon that she designed back in 2016 that I’ve offered to the world to share, to have a symbol for an awareness ribbon for the community. I think will have also some more articles coming out and podcasts coming out and we’ll just try to get our voices heard as much as we can.

Cristina Might: Our partners at UDNI, the Undiagnosed Diseases Network International, and the little hum Foundation are putting on Undiagnosed Day events. And I was trying to find the website because I don’t remember. I think it’s something like undiagnosed day or undiagnosed something, but there’s a symposium, there’s different speakers, and hopefully this will continue to gain momentum because this Undiagnosed Disease Day, I’m commemorating my son and others, like him who have passed away on the odyssey, and hopefully remembering that there’s still so many here that are worth fighting for. And hopefully, while Gina is the sweet, I’m the sour. I’m going to kick a few hornets nests and hopefully get other people just as motivated to create something because everything, all the pieces are there. We just need people to work together. So hopefully this is the year that we don’t take any more excuses as answers within the undiagnosed community. And we make some change.

Daniel Levine: What advice would each of you offer for people who are undiagnosed? I’ll start with Gina.

Gina Szajnuk: My advice is just to listen to your gut and if something feels wrong, I think you have to find and continue to find a good medical team that will listen to you. That will be your partner on this journey. I think many times, and when I talk to many patients, they feel like they’re not heard. And I feel like you just have to keep going, keep fighting. As I’ve said before, you only have one body and one life. You’re worth fighting for and your children are worth fighting for, your parents are worth fighting for. My advice is just to keep going and not give up and every day, wake up and fight and try to work that diagnostic odyssey to your advantage until you can get to the person that will listen to you and help you on your path.

Cristina Might: I feel like I’m talking out of two sides of my mouth. On one side, part of me wants to say it’s a marathon, not a sprint. When it comes to your odyssey, I feel like so many families burn themselves out and get discouraged when they don’t see results right away. And you have to basically document, document, document. Like Gina said, you have to stay on top of people. You need to keep finding resources, but it’s step by step. You know, how you eat an elephant one bite at a time, right? It’s the same thing with undiagnosed. When I look back and look at everything we managed to accomplish and do with Buddy, it that did not happen overnight. That was the culmination of almost 13 years of effort. So, each day celebrate those small victories. Remember to sleep, eat, take time for yourself and for your families, love and hug your little ones, your loved one, because time is that most precious of all resources and we never have enough of it. So, I don’t know, just don’t give up hope. Don’t be afraid to ask for help because there are amazing resources like RUN, Gina, Amy Clugston, Alene, so many others within the undiagnosed community that are there, the UDN as well, that are there to help undiagnosed patients and their families. But give yourself some grace and, hopefully, if today is a hard day, wake up tomorrow and keep fighting.

Daniel Levine: Gina Szajnuk, co-founder and executive director of the Rare and Undiagnosed Network and Christina Might, co-founder and acting executive director of the Undiagnosed Disease Network Foundation. Gina, Christina, thanks so much for your time today.

Cristina Might: Thank you, Danny.

This transcript has been edited for clarity and readability.

 

 

 

 

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