Rare Disease Day 2025 – PediaCast 573

Show Notes

Description

  • Drs Beth Kozel and Vidya Sivaraman visit the studio as we consider rare diseases and the 300 million people they impact (as a group, they aren’t so rare!). February 28 is Rare Disease Day, which seeks to raise awareness, improve understanding, and provide support. We hope you can join us!

Topics

  • Rare Diseases
  • Rare Disease Day 2025

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Episode Transcript

[Dr Mike Patrick]
This episode of PediaCast is brought to you by Genetics and Genomic Medicine and by Pediatric Rheumatology at Nationwide Children's Hospital. 

Hello, everyone, and welcome once again to PediaCast. We are a pediatric podcast for moms and dads.

This is Dr. Mike coming to you from the campus of Nationwide Children's Hospital. We're in Columbus, Ohio. It's episode 573.

We're calling this one Rare Disease Day 2025. I want to welcome all of you to the program. So, this is our very first episode of 2025, so I want to wish all of you a Happy New Year.

And I was reflecting on previous New Years on PediaCast, and it struck me, and I actually laughed out loud, like, literally, when I thought about this, back in, I think it was either 2007 or 2008, because we started this podcast in 2006. So, we were one of the very first pediatric podcasts out and about. In fact, I think we were probably one of the first medical podcasts back then, because podcasts really got their start back in 2005.

So, we just started, you know, a year after that, and have been podcasting, you know, all of these years since. And it was 2007 or 2008 when I wished everyone a Happy New Year, and in particular, I welcomed all of the folks who had received an iPod, not an iPhone, an iPod for Christmas, and welcomed them because, you know, there weren't a ton of podcasts out there like there are today. And I thought, you know, if I was a parent, and I received an iPod for Christmas, I might look up and see if there's any shows on child health.

And so, I welcomed all of those with brand new iPods. And if there's anyone who did get new tech this year, and you're listening to a podcast for the first time, and we are, you know, one of your first listens, welcome, and congratulations for joining the digital revolution. But anyway, I totally digress.

Boy, this is a great way to start the new year. We do have an ambitious production schedule for you. We're really excited to bring you another year of content.

And this year, we're actually going to have more episodes, more topics, but we need your help in filling the schedule. So, if you have an idea for PediaCast, please head over to pediacast.org. That's our contact page, or that's our landing site.

And we have a contact page at the landing site, pediacast.org, and just fill out that form, send it in. We do, I personally read each and every one of those. If you do have a topic idea, let me know, and we'll try to get it into the lineup.

Again, we have more spots this year. So, hopefully you'll help us to fill the schedule, and we'll be able to talk about the things that are important to you. We're kicking off the new year with a look at rare diseases.

Here's the thing, though. There are so many rare diseases, like literally thousands of these disorders. So, even though each rare disease impacts a small number of people, when you combine them, it's a very large number.

Like, 300 million people worldwide are impacted by a rare disease. And so, lots of people are affected by one of these disorders or another. In fact, it's likely that you know someone who is impacted by a rare disease.

There are that many of them out there that it's likely we each know someone. But again, each one is rare, and so there hasn't been as much focus or research into these disorders because there's not a large pool of people that that would impact. And because we are in a capitalist economy, it does mean that our healthcare is driven by profit in many cases, and that includes research and funding for pharmaceutical research on rare diseases.

And so, these folks, you can imagine, that's just frustrating that you have a disorder just like someone, you know, your neighbor has a disorder, but theirs is a common one. And so, it's easier to, you know, get help and have, you know, research about your disease and multiple treatment options. And that is a luxury, really, for folks who are impacted by rare diseases.

So, today we are going to talk about rare diseases as we try to raise awareness and provide support and shining a spotlight on rare diseases. And that actually is also the goal of Rare Disease Day, which will be coming up next month, February 28th, to be exact. That is Rare Disease Day here in the United States and perhaps worldwide.

It might very well be around the world. But it is going to be an important day, again, to raise awareness, provide support and shine that spotlight on rare diseases. So, we're getting a little bit of a jump on it because I wanted this episode to be out there and well-established and available for everyone to share on Rare Disease Day.

So, we have lofty goals, but we do have two really terrific guests joining us this week as we strive to make that difference. Dr. Beth Kozel, she is a geneticist at Nationwide Children's Hospital with the Division of Genetics and Genomic Medicine. And Dr. Vidya Sivaraman, she is a pediatric rheumatologist, also from Nationwide Children's. Don't forget the information presented in our podcast is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for specific individuals. If you are concerned about your child's health, be sure to call your healthcare provider.

Also, your use of this audio program is subject to the PDACAST Terms of Use Agreement, which you can find at pdacast.org. So, let's take a quick break. We'll get our expert guests settled into the studio, and then we will be back to talk about rare diseases.

That's coming up… right after this. 

[Dr Mike Patrick]
Dr. Beth Kozel is Chief of Genetics and Genomic Medicine at Nationwide Children's Hospital and Director of Constitutional Genomics Translational Research in the Steve and Cindy Rasmussen Institute for Genomic Medicine. She's also a professor of pediatrics at the Ohio State University College of Medicine. Dr. Vidya Sivaraman is a pediatric rheumatologist at Nationwide Children's. She serves as Director of Quality Improvement in Rheumatology at our hospital, and she is an associate professor of pediatrics at Ohio State.

They both have a passion for raising awareness and supporting children and families impacted by rare diseases. That is what they're here to talk about, Rare Diseases and Rare Disease Day, which is coming up on February 28th of this year. But first, let's offer a warm welcome to our guests, Dr. Beth Kozel and Dr. Vidya Sivaraman. Thank you both for visiting us today.

[Dr Beth Kozel]
Good morning. Thanks for having us.

[Dr Vidya Sivaraman]
Good morning. Thank you so much for having us on the podcast.

[Dr Mike Patrick]
Yeah, we really appreciate both of you stopping by today. So, let's start with you, Beth. What do we mean by the term rare disease?

[Dr Beth Kozel]
It's a great question. So interestingly, the sort of definition medically of what a rare disease is depends on where you are. In the U.S., we defined a rare disease as a condition that affects fewer than 200,000 people in the United States. So, if you take the whole population of the U.S., there has to be less than 200,000 people affected by the condition. That means when you sort of take those things individually, it can be small numbers in terms of people with a particular rare disease. But when you think about all the rare conditions together, that's actually pretty common.

So that actually ends up being 60 in every 100,000 people in the U.S. have one form or another of a rare disease. So that's one of the things that we're thinking about in rare disease is that individually these things are rare, but together we're quite common and part of the things we're interested in are sort of celebrating that uniqueness.

[Dr Mike Patrick]
Yeah, yeah. So, each individual rare disease is rare and not very many people are affected. However, if you are one of those people, then that means the world.

And if your family member is one of those people, and then it is likely that you might know someone who has one of the rare diseases because when we put them all together, as you said, one statistic I saw was like 300 million people worldwide are impacted by a rare disease. So not so rare, but as individual diseases they are, which I suspect can impact research into treatments. Just if you're from a drug company lens and you are trying to make a profit, then there might be less incentive for you to go after individual rare diseases, which I'm sure is very, very frustrating.

Is that something that you that you encounter, Beth?

[Dr Beth Kozel]
Absolutely. So across rare conditions and especially given the fact that we're learning more and more about new conditions all the time, that inviting pharmaceutical companies and otherwise to sort of participate in thinking about these conditions is harder compared to something like diabetes or high blood pressure that's sort of rampant everywhere. Really thinking about that sort of smaller community of people means different types of research studies, different types of funding for those sorts of things.

And because they're sort of outside the norm of what a lot of companies do and sort of where they want to put their efforts, we've really had to sort of work with companies and organizations to help raise awareness that tackling these sorts of things is good for people and is a worthy investment.

[Dr Mike Patrick]
Yes, yes, absolutely. It seems that the number of rare diseases that we have defined is growing by the year. And so, if we look at compared to maybe a decade ago, there's a lot more rare diseases that we have identified.

Why is that? Why are they increasing?

[Dr Beth Kozel]
I would definitely agree with you. And my colleagues and I are definitely feeling that in terms of our busyness. But yes, I think that the number of conditions, at least in terms of our ability to define them clinically, meaning that we could see a person in a clinic and say, hmm, they have these unusual features.

That part hasn't really changed too much. But our ability to say, oh, I know what causes these features in terms of “are there gene changes that are responsible for that” has changed dramatically. So, we think that we have around 20,000 genes total.

And as a medical community, we have sort of solved around 7,000 of those, which means we've come a long way. We still have a long way to go. But because of the sort of new technologies that we're able to use in genetics and genomics right now, we're getting further and further in being able to say, OK, this set of medical problems seems to be due to a change in this gene.

And having that information allows us to do exactly what you just talked about in terms of trying to even begin to think about targeting therapies and other things toward that. Because if we know we don't know what causes it, it's really hard to fix it. But now that we're putting names to that with that growth, we're able to do a lot more.

Yeah.

[Dr Mike Patrick]
So, they're not necessarily new diseases. They've probably been around for a very long time. And we just now have a name for those diseases, which I'm sure is very helpful for families because it's frustrating when you know something is going on, but you can't quite put your finger on it.

[Dr Beth Kozel]
Absolutely. And it's allowed us to sort of distinguish things that previously might have sort of been lumped into sort of a group of people who have certain things in common. But to be able to say, oh, no, this sort of subset of people actually has a little something a little bit different.

And again, in that situation, it changes the name a little bit but might also sort of change our sort of therapeutic strategy and how we might help take care of people.

[Dr Mike Patrick]
You had mentioned Rare Disease Day. Tell us about that. What is Rare Disease Day?

[Dr Vidya Sivaraman]
Yeah. So Rare Disease Day is actually a global event commemorating patients with rare diseases, their caregivers, families. And so, it's actually celebrated globally.

And a lot of people don't know that. I didn't know about that till a few years ago. And every year it's observed on the last day of February.

So, February 28th or in a leap year, February 29th. So, you're really trying to celebrate, you know, how rare these patients are and, you know, kind of bring them together. And so, events are held throughout the world to commemorate Rare Disease Day.

One of the big events, for example, is at the National Institutes of Health in Maryland to commemorate some of the research that's going on with these diseases and various children's hospitals and organizations around the country. One of the organizations that highlights this is called NORD, which is the National Organization for Rare Diseases. So, every year they actually identify some kind of a theme or a common topic for patients with rare diseases.

And this year's topic, interestingly, is more than you can imagine. And I really like that topic because it really kind of highlights that there's so much more than you can imagine that actually is common to these diseases. So, for example, what that highlights is, you know, as a rare disease, you may think I am the only person or I am one of very few people with this condition X, you know, and so you may just feel very alone.

But here this is actually highlighting that you have you might actually have things in common with other patients, whether its struggles related to getting a diagnosis, getting a treatment, dealing with a long-term or lifelong disease, and so on. So that's really a big part of what we're trying to highlight through this event.

[Dr Mike Patrick]
And I love that it's February 28th or 29th on leap years because those literally are the two rarest days of the year, right? Absolutely. They happen the least often.

So here at Nationwide Children's Hospital, we are going to be celebrating our seventh annual Rare Disease Day. Tell us a little bit about what we are doing to celebrate kids and families impacted by rare diseases.

[Dr Vidya Sivaraman]
Yeah. So, this is actually something I've been passionate about, you know, throughout my career. And in rheumatology, our focus is a little bit different than with genetics.

So, we deal with a lot of autoimmune diseases and diseases of the immune system. And we're finding that many of those actually have a genetic basis also, but in some cases they don't. And so, what we've done is really try to bring together these families with kids that are impacted by these diseases.

And so, in previous years, we've had over 200 people, whether it's patients, caregivers, family organizations, researchers, healthcare professionals, really anyone that has any interest with a rare disease come together for this event. So, this year, it will be our seventh year celebrating this event. We're going to have the event on Saturday, March 1st, in the morning from 9 to noon.

It is primarily for patients and caregivers. So, it's very much focused towards, you know, a lay audience where we want to make it not technical, not, you know, full of medical jargon that can sometimes make these patients feel lost. And so, our program, I'll highlight just the two major aspects of the program.

So, we usually have a keynote speaker, somebody who can highlight in some way and inspiring story or an inspiring aspect of the rare disease journey. And so, this year, our keynote speaker, we're excited to welcome Dr. Cara Ayers from Cincinnati Children's. And she herself has been a very strong advocate, patient and researcher for rare disease.

And she will be speaking about resilience within the rare disease community and how you can support your child after a diagnosis of a rare disease and also for people with disabilities. So that's one major component. And then she actually will also be giving pediatric Grand Rounds the day before on Thursday, February 27th, as part of our rare disease awareness for medical professionals.

And then the second part of our patient event, which we have every year, is actually a patient panel. And what we found is by having a panel of patients with a variety of rare diseases, we get to hear different aspects of their individual story. And that could be their challenges with getting a diagnosis, challenges with getting treatments, just day-to-day things that they're dealing with their child.

And so that's often really powerful for families to hear it from another patient's perspective. So that's really been usually the most popular part of our event every year. And so, we're excited to bring that back.

[Dr Mike Patrick]
Yeah. And I can tell you're excited about Rare Disease Day. And I think it's an important thing.

Can you kind of walk listeners through why this is just such an important and exciting thing?

[Dr Vidya Sivaraman]
Yeah. And so, I think the biggest thing that we really want people to realize is that patients with rare diseases often feel very isolated because they feel there's only so many people in the world with this disease. Nobody's going to study more about it.

I'm never going to have an answer. I'm never going to have a treatment. And as you alluded to earlier about, you know, drug companies, for example, finding treatments.

So, one important statistic is that over 95% of rare diseases do not have an FDA-approved treatment. So, they're really very much isolated in the sense of, you know, trying to get a treatment. The other part is their diagnostic journey.

So, it's been mentioned that some patients on average can take over seven years to get a diagnosis. They may see 12 to 14 medical professionals before they get a diagnosis. And so, they often feel like this is kind of a never-ending process to try to get, you know, some kind of answers.

And so, what we're trying to do as part of this event is really to help these patients and caregivers to find some of that common ground and be able to kind of interact with each other and find some kind of support. One example for that would be a patient with a recent or new diagnosis of a rare disease. They can often connect with somebody who may be older or further along in that journey and really help get that support, which can be very valuable at that time.

For example, I'll share, you know, just a couple of anecdotes from previous years. We've had patients that became such good friends from meeting at this event. We have two boys, for example, that will go to each other's birthday parties.

They go to summer camps together. They even schedule their medical appointments at the same time so that they can come to the same time and get to hang out in the waiting room. So, you know, this has really built almost like lifelong friendships for some of these patients.

Sometimes patients feel that nobody's even heard of the disease that they have. And so, to actually be at an event and sitting next to another kid who has not only heard of it but actually has the same condition can be just powerful for these families. The other thing I highlight is that caregivers can actually gain a lot from attending this event.

Caregivers feel that same sense of isolation and that sense of burden, which can sometimes be very overwhelming and take a huge toll for the parent and even siblings. And so, to address that issue, we've actually included topics like mental health. Transition to adult care are some examples of topics we've used in the past to really highlight what we can offer.

[Dr Mike Patrick]
And not only in terms of celebrating each other and the families, we're also going to be highlighting some specific services at Nationwide Children's Hospital during this year's celebration. And I just wanted to just talk a little bit about each one of these. The first one is Prater-Willi.

Dr. Beth, can you explain what that is?

[Dr Beth Kozel]
Yes, thank you. I'm happy to. I think it's important to note that almost all of the specialties we have here at Nationwide Children's see people with rare conditions.

And it would be impossible for us to sort of highlight all of the exciting things going on here for that. So yes, we wanted to start this year with sort of putting a focus on some of the really cool and exciting things going on in some of our clinics. And Prater-Willi Clinic is one of the clinics that we're excited to talk about.

So, if you've never heard about Prater-Willi syndrome, it is a rare genetic condition that children with this condition often have low tone when they're born. So that means they have a hard time sort of holding their head up. They have poor appetite.

They don't feed well. But interestingly, then that changes over time where they have this sort of change in their demeanor such that then instead of being hard to feed and really irritable, they actually get really, really hungry. And I have this problem where they have excessive eating to the extent that sometimes families have to lock up food and do different things like that.

They have other sort of developmental conditions associated with their growth and behavioral features that are common in that patient population. And so, their health concerns based on their genetic condition covers a lot of different specialties within the hospital, which can make it hard for families to need to come on Tuesday to see this doctor and the next Thursday to see that doctor. And so, what the hospital has done is created a unifying clinic in which we actually bring all the doctors together in the same place so that families who are affected by Prater-Willi can bring in their family member to be seen by everybody at once.

And that we call an interdisciplinary clinic. And it means that the family's together on a team with a set of doctors. So in this case, that type of clinic involves endocrinology, which is hormone doctors, the genetic doctors who help with both the genetic diagnosis and sort of the what to expect from this rare condition standpoint, the neurologists, the sleep doctors, psychologists, and people that are engaged in nutrition and sort of the feeding aspects of the condition as well as social work to sort of tie together all of the resources that are needed from a support standpoint. In addition, it brings in people who've really spent a lot of time reading and growing and being educated, and in fact, the world's educators in some cases on this condition.

One of the things that's really cool about this clinic besides this sort of interdisciplinary practice is that like that thing that we talked about, 95% of rare diseases don't have treatments is that they actually are starting to have treatments. And so, they are actually in the process of running several phase three studies for some of the health aspects of Prater-Willi, most of which are associated with the sort of overfeeding part of the later part of the condition that causes a lot of health concerns for people as time goes on. But that means that those patients that are involved in that clinic are able to be at that cutting edge in terms of trying these medications before, you know, they go mainstream that people get the opportunity to sort of be engaged in that.

Yeah.

[Dr Mike Patrick]
And another one that we'll be highlighting is metabolic bone disease. Tell us about that one.

[Dr Beth Kozel]
Yeah. So this clinic is, as opposed to Prater-Willi, which is based on a single specific condition, this one actually takes into account a group of patients that have a range of conditions affecting how the bones grow in terms of how they develop to begin with, and then what we call sort of metabolism, which is how our body sort of moves bone product around over time. They see over 250 new patients per year in terms of the different diagnoses that they see, most of which are children, but we follow some of those folks later on and take care of them for the range of those conditions.

Same sort of thing from Prater-Willi in the sense that there are multiple doctors of different specialties that come together to take care of these folks. So, genetics is involved largely at the diagnostic standpoint, and then folks that are within the nephrology, the kidney actually is involved in a lot of the way we move calcium around in our body, and other folks associated with those conditions. Some of the conditions that they take care of in that clinic involve a condition called osteogenesis imperfecta, which is a gene change that happens where the bones are excessively brittle and can break.

And then there are other conditions that are associated with how bones grow and their actual structure. Interestingly, like the Prater-Willi case, we're actually starting to see some new therapies come online for those sorts of things as well. And so, while not every family may decide that those medicines are for them in terms of what they'd like to engage in, in terms of the growth and metabolism of their bones, the exciting thing is that there are now options.

And so having doctors that are there that can sort of help talk people through the pluses and minuses for getting on these therapies, what that would mean to them, what the possible positives are, where the challenges might be, and how that might affect where their life goals are is really important of that sort of whole person care. Yeah.

[Dr Mike Patrick]
You know, as you're going through this, Prater-Willi and osteogenesis imperfecta are things that I think some more folks have heard of those than some of the other ones. And I think that's also an indication that even before modern genomics, we recognized patterns. And so maybe we didn't know exactly what caused these things, but we could start putting those patterns together.

And so, Prater-Willi and osteogenesis imperfecta are things that have just been around a lot longer than some of the newer ones. Another one that I've heard of before, so I'm not being a geneticist or a rare disease expert, lets you know it's probably been around for a while, and that is scleroderma. And then also a CRMO, which stands for chronic recurrent multifocal osteomyelitis, which is a mouthful.

So CRMO is what that is called. Dr. Vidya, tell us more about those things.

[Dr Vidya Sivaraman]
Yeah, absolutely. So, these are a couple of rare diseases that we take care of within rheumatology. So, these are more on the autoimmune side of things and may not always have a genetic basis for these.

So, scleroderma, basically the term itself means tight skin. And so, this is a condition where there's an autoimmune issue, where there's skin tightening that can happen. And the same kind of tightening can happen even within internal organs, which can be pretty scary.

So, there is a localized form where it mainly causes tightening within the skin, the joints, so just underlying structures. It can also happen on the head and the face. And so, as you can imagine, that can be disfiguring.

In kids, it can affect their growth. So that can be a huge issue if it goes untreated. And so that's called the localized form, which fortunately is more common in children.

But there's an even more serious form called systemic scleroderma, where they actually have more internal organ involvement. And fortunately, that's less common in kids, but still, something to recognize and treat. So, as we alluded to with other conditions, these patients often go 12 to 14 months on average before getting a diagnosis.

So, if you can imagine for a child's growth and development, that can be a huge amount of time if there's a delay in diagnosis. And so that's one of the reasons we really highlight for basically all providers, even primary care providers, to be aware of these conditions, because you want to make sure you recognize them early and get them to appropriate therapy. So, for these conditions, we don't have multidisciplinary clinic, as was mentioned for Bone Clinic and Prader-Willi Syndrome.

But we do work with a kind of a multidisciplinary group. So, for example, with scleroderma, we work closely with our lung doctors, because when they have a systemic form, they can have involvement of the lungs, the heart, and even the kidneys. So, we do work closely with our pulmonologists or lung specialists.

And then we also partner with dermatology, because a lot of them present with skin issues early on. We also work with specialty pharmacies, psychology, and social work to really ensure best outcomes for these patients. And then with scleroderma, fortunately, there is a multidisciplinary scleroderma specialty clinic at The Ohio State University.

So, when these patients are ready to transition to adult care, we're able to send them on to Ohio State to continue their care. And then as far as treatment for scleroderma, again, while we don't have specific FDA-approved treatments for children, fortunately, we have treatments that are used maybe for arthritis that we can sometimes adapt to treat these children with scleroderma. So, we are able to offer some treatments.

Another approach that I would highlight is basically becoming part of a registry. So, when we want to study these patients with rare diseases, we often have to collect multiple patients with that certain condition to even be able to study them over time. So, we are fortunate to be part of an international collaborative, which is called the Childhood Arthritis and Rheumatology Research Alliance, or CARA.

And through this, we have subgroups that study each of these rare diseases. And so, I'm part of the scleroderma subgroup for CARA. And so, we're able to bring some of that research to these patients and say, oh, another center is working on this particular aspect of research or this particular treatment.

And so, we can kind of learn from each other. The other area is that we also partner with patient foundations. So, the Scleroderma Foundation is very active in Ohio.

We're very fortunate to have a great foundation support here locally. And so, I've been part of their team as a medical liaison. And then I also help organize national patient conferences for kids with scleroderma.

And then moving on to the other condition you mentioned, which is the CRMO, which is Chronic Recurrent Multifocal Osteomyelitis. So, this is a rare bone disorder, and it involves inflammation in the bones. So, it's not an infection, but it's inflammation that's happening in the bones.

And again, we don't know what causes it. And another term that's used for it is chronic non-bacterial osteomyelitis. So often, osteomyelitis is an infection in the bone.

But in these patients, there's no sign of infection, but you're seeing that inflammation within the bone. And again, here also, there is no FDA-approved treatment specifically for CRMO, but we have certain treatments that have been studied by the groups from CARA, which was the research organization that I mentioned. And so here also, we have patients actually with both of these conditions that travel from around the region.

So not just all over Ohio, but we have patients from West Virginia, Kentucky, sometimes even other states that will actually travel to be able to get that multidisciplinary and specialty care. We also partner with the Bone Clinic because one of the treatments for CRMO, interestingly, is a medication that's used to treat osteoporosis, and it actually helps with bone healing. And so that's another area that we're able to partner with the Bone Clinic and provide specific treatments.

[Dr Mike Patrick]
Yeah, it's just a wonderful thing that you can really highlight these four conditions for Rare Disease Day here this year. Is that something that you kind of rotate through? So next year, there'll be four different things that are highlighted?

[Dr Vidya Sivaraman]
Yeah, this has been a new… We're trying this this year, so it's going to be interesting to see where we're going to highlight a few specific clinics. Because as Dr. Kozel mentioned, pretty much every specialty and every clinic at Nationwide Children's sees rare diseases. And so, this way, we're able to kind of focus on a few diseases, focus on those patient organizations, and invite them to be part of the event and kind of connect with their audience.

[Dr Mike Patrick]
I love that because there's, of course, going to be something for everyone who's impacted by a rare disease during the course of the day. But by highlighting those four, it does make it a little more likely that you'll get folks more than one who has a particular condition. And then, as you said, that can lead to lifelong friendship and support and networking and all of those things.

So, I think it's a great idea, and hopefully it works out and you can continue to highlight specific rare diseases on Rare Disease Day. Dr. Vidya had mentioned that there's often a delay in the diagnosis of rare diseases, which can be extremely frustrating for the family, for sure, but even for primary care doctors who also know that there's something going on. And you may have referred to this specialist or that specialist, and nobody can figure it out.

And that could become frustrating really fast. Beth, can you explain why there is typically a delay in the diagnosis of these disorders?

[Dr Beth Kozel]
I think in general, it's because they're rare. And so, lots of people haven't necessarily heard of them. And so there isn't necessarily a, if this happens, do this, that's in everybody's sort of repertoire of things.

I think that the other piece is that it's changing rapidly, like we were saying. So many of these conditions didn't exist as a sort of known entity three months ago, one year ago, and sort of the ability to sort of keep up with that with the global speed at which we're working can be difficult. But I would say that if folks can get to us in genetics, we have a lot of really great tools to start to bring that together.

So, I personally, on a research side, work with a group of patients who have a condition called Williams syndrome, which is another rare disease. And when we've studied that within our patient population, what we've seen is that as technology has gotten better, the age of diagnosis has come down significantly. So, it used to be back in the day, and we'll say the late 1900s in terms of the late 90s is when the first test for that condition came to be a thing.

But at that time, a doctor had to specifically know and suspect Williams syndrome to do that test, and they had to send basically the Williams syndrome test. And so, the people who knew what Williams syndrome were could send that test and get that done. But in specialties or individual doctors who had not seen a person with Williams syndrome before, they didn't necessarily think to send the test.

But now what we have are broader genetic tests that sort of cover the whole genome at the same time. And so that means that we can send sort of a universal test that covers hundreds and thousands of conditions simultaneously. And with that, if a person, a child goes into their doctor and they say, something isn't right here, I'm suspicious that there's something genetic going on, even if they don't necessarily at that moment know what the answer is, they can still send that test.

And with the information and the data that comes back from that, we can start to put those pieces together where we say, oh, there's a gene change here in this gene, and that tends to go along with people who have these types of symptoms, and that's a match. And so, it'll, that sort of advance in the technology is allowing us to do many more of these things simultaneously. And so, like in our condition, in Williams syndrome, like I said, back in the days, the average diagnosis was, you know, six, seven, and now we're down to under one year with that diagnosis.

So, people having that information sooner, able to sort of plan and sort of chart a course for their family member at an earlier period of time, largely due to these sorts of improvements in our technology. Yeah.

[Dr Mike Patrick]
When a family maybe reaches out to their doctor and lets them know, you know, we're really concerned about this, and then you talked about a universal test that could be ordered that's looking at the entire genome, you know, to find what specific matches there might be. That sounds expensive. And I'm wondering, is that something that insurance companies generally pay for, or is there a financial burden on families who are struggling to figure out what's going on with their kiddo?

[Dr Beth Kozel]
Oh, it's a really good question, and it is a largely moving target. I will say in general, the sort of price and of these technologies as they become more common is coming down. I will also say the number of sort of research studies that have shown these sort of broad tests are the way to go in terms of making diagnoses and putting more and more of those studies into the literature is causing insurance companies to understand that supporting these diagnostic tests sooner leads to better care of people sort of under their umbrella, and so we're actually seeing some uptick in the willingness of insurance companies to support us in doing those tests. So yes, in terms of what it is, it is something that we're needing to do what we usually call sort of preauthorization, where we go to the insurance company and say, hey, this is what we have going on, would you be willing to pay for that and jump through some paperwork hurdles in terms of the back and forth with those things.

There are additional supports outside of that for many of our patients that even if the insurance company says no, we have some types of resources that we can get to support that, but we are very much doing sort of a back and forth with patients and helping them understand what that would mean in terms of a financial burden for them. So, in general, we don't go ahead and send the test until everyone agrees that this is sort of doable for that individual and their family based on the math of their personal insurance and the things that affect them, but there isn't always a 24-hour process. It's something that we have to work through a little bit, but we're getting better and better at that, and like I said, the data is getting better and better such that we're starting to see some much better uptick for incorporation of that testing.

[Dr Mike Patrick]
Yeah, yeah, that's encouraging. I'm sure we have a long way to go, but at least folks recognize the issue and are working it. If primary care physicians have difficulty in terms of what to order, how to get it preauthorized, is that something that they can contact the genetic center, or how do primary care docs figure out what path to take?

[Dr Beth Kozel]
No, that's a great question, and I would say I'm actually new to Nationwide, so I started here early last year, and we're putting a lot of play changes together in our division so that we can help support people with rare diseases better. One of the things that we're doing is really bringing a lot of those diagnostic tests to the hospital and getting those diagnoses sooner so that hopefully even by the time a new baby makes it out of the hospital to their pediatrician, they actually come with that information in hand, and so sort of bringing that to the very beginning stages we think will help, especially in a lot of our kids who sort of end up in the hospital as part of their journey into life. Then on the sort of outside side, genetic testing as it relates to sort of whole genome probably should really only be done in collaboration with a genetics professional. There's a lot to be understood as it comes to understanding one's whole genome, and so that sort of partnership with folks that sort of think about those challenges every day can be really helpful.

So, we in genetics work with a team that helps us with those pre-authorizations and the sort of paperwork parts of things but also works with sort of genetic counseling with the families to talk to them about what they might learn from this test. So there's a significant part of education that actually goes into genetic testing that we call sort of pre-test counseling, where we talk through what the technology can do, what it can't do, what it would mean if you had a positive test, what it would mean if you had a negative test, and really make sure that people are entering into that type of testing with their eyes open in terms of the types of things that you can find from it.

And so, our goal would be, you know, that families who have a concern that their child may have a rare condition start with their pediatrician, because not everything turns out to be rare, and sometimes there's stuff that can be done in primary care that will help. Sometimes we actually need folks to see some of those specialists beforehand, and we talk about that to some degree as sort of a delay, but it's actually in some cases a necessary delay, because the way genetic testing works is that we take this piece of DNA that comes from your blood or saliva, and we basically, if you think about it as a shelf of encyclopedias worth of books, we read every single letter in that shelf of books and look for typos. And you can imagine across that entire thing there's going to be a lot of typos, a lot of gene changes that are just part of the general variability between me and you, and what we have to sort out is which ones of those sort of typos or misspellings is associated with their condition. The best way we make that match in terms of what we call the genotype, the gene change, and the phenotype, which is the patient's appearance and medical problems, is that if we actually have a good definition of their medical problems.

So, for example, if what the pediatrician knows at the beginning is that the child has a heart murmur, actually having had an echocardiogram to say the heart murmur comes about due to this change in the structure of the heart can actually be helpful then for that better pairing of information between the genetics and the heart change, because there may be a hundred genes that affect how the heart works, we want to match the one that causes their specific heart problem.

So, there's a period of time in which we work with, in collaboration with the specialists in other organ systems, and then we put that together with the genetics. So, and like I said, what the order, whether they see the, you know, for example, the cardiologist first and then the geneticist or the geneticist and then the cardiologist, like it ends up being sort of a team approach where everybody puts their sort of relative smarts into the mix to try to bring that diagnosis together. But in terms of the pediatrician, if they want to just make that patient's referral to come and see us, we're working our best to get people in as sort of as fast as we can in order to make that process work smoothly for people.

[Dr Mike Patrick]
Yeah, so you would think, well, could we get the appointment but then get the blood work and the pre-authorization thing going, but that's a good point. You really want to know more information, so you're not just ordering haphazardly, you're ordering a little more focused, which then that also is helpful from a financial standpoint too. So, as frustrating as that must be for parents, because there are these delays and sort of hoops that they're jumping through, and now I have to see this person and that person before we can order the blood work, but just sort of understanding the complexities and sort of having patience with one another and empathy and all of those things, I'm sure it's not an easy task being in your shoes at times, I would imagine.

[Dr Beth Kozel]
It is, and there are definitely ways that we can do better, and so we've really tried, I've had a lot of meetings since I've been here, sort of thinking about what are the ways that we can improve those processes, certainly on the things, the paperwork parts of things, how can we do that better, faster, and by people who are sort of really good at that aspect of the work, and then how do we coordinate best with our partners in other systems so that we aren't saying, oh, they're seeing this doctor, and then six months later they're seeing this doctor, how do we sort of get those things closer in time and with better communication between those teams so that it becomes much more seamless, and I think that we will see, you know, over the next few months, over the next year, that we really start to see that sort of coming together in a really sort of meaningful way. I do still put a lot of hope in terms of a lot of the work that we're doing at the sort of very beginning at the diagnosis phase for those folks, because I do think the earlier we get a diagnosis for people, the earlier they can start using that information to make medical decisions, and I'm hoping if we do a really good job of that, it will actually put less burden on that sort of the outpatient side of trying to get people in later on.

[Dr Mike Patrick]
Yeah, yeah. Dr. Vidya, can you kind of walk us through what this must be like from the parent standpoint, and how can they best advocate for their kids during this difficult journey?

[Dr Vidya Sivaraman]
Yeah, absolutely. So, this can be, as I said, a very big challenge for parents and caregivers, and, you know, so one way I kind of explain that to families is I always tell parents, like, you're the expert in your child. Like, this is a condition that could have, you know, as Dr. Kozol mentioned, they could have heart issues or skin issues or lung issues, and sometimes these happen over time. So, parents are noticing, hey, this, you know, this child just isn't the same as their brother or sister, something is changing a little bit. Talk to your pediatrician. It's okay.

That's the best way that you can advocate for your child. You know, look out for those things. Take pictures if you see certain things showing up or new symptoms or new signs of things.

And I also compare it to, like, connecting the dots sometimes. So, you have all these different little dots, and sometimes to get that rare disease diagnosis, it's kind of a unifying picture. And while you might see the heart doctor and they tell you what the heart defect is, they may not be able to tell you if there's other organ systems affected.

So as a parent, the biggest thing you can do is kind of just monitor, you know, those symptoms. As I said, it can be pretty long and stressful. The other big thing is trying to find a medical home.

So, in a way, it is, you know, you might be seeing your pediatrician, you might be seeing the heart doctor, but if you're starting to see other specialists, try to really build on that medical home where you have one place and, you know, maybe one physician kind of directing all of that. And so, for us, often in rheumatology, if it is an autoimmune condition, like scleroderma that I mentioned, we're kind of that quarterback, kind of we're the ones having to direct all of the others to try to, you know, come up with a unifying treatment plan. And that's something that's actually been looked at like, you know, nationally and even worldwide with this, you know, rare disease approach.

And so, NORD, the organization that I mentioned, has actually established like centers of excellence around the country that can actually be a medical home. And we're fortunate that Nationwide Children's was actually designated as a rare disease center of excellence in 2021. And so there was this competitive application that we went through.

And so, we're one of just 40 centers around the country as a rare disease center for excellence. And so that helps us to kind of form some of this unified model for diagnosis, treatment, and research for rare diseases. So that's definitely something I would highlight.

Other things that patients can do, and parents can do is, I think, like you said, it does involve some amount of that patience, because, again, things may show up over time, and you're trying to connect those dots. Sometimes I compare it to the TV show House, like Dr. House has to kind of solve that medical mystery. So, we're sometimes having to do that.

Another aspect, just in terms of medical education, even we're at that point where medical providers, a lot of the training is really to diagnose common conditions, and not so much to diagnose rare diseases. So, one analogy is that in medical school, you're taught, if you hear hoof beats, think of horses and not zebras. But these patients are actually those zebras.

And so, the zebra is actually a symbol for rare disease. And this is a way that we highlight to medical providers, patients, and families that these are rare. So, bear with us, it does take time to get a diagnosis.

But there are people looking out for you that want to study your disease and want to be able to help you. And we have come so far, and we're coming so much faster in the coming year.

[Dr Mike Patrick]
Yeah. And I would imagine that if you have a kid who is maybe, say, see this doctor, and then the families really want to take matters into their own hands, which is totally understandable. And so, you're like, we're not getting anywhere.

So, you switch to a different doctor, and maybe a third doctor. And now you go to the ER because you think, oh, this is a children's hospital, certainly they can figure out what's going on. And then six months later, you're back in the ER, and then do an urgent care, and then do a different doctor.

Like if there was a way, you know, someone could look down and say, wait, this kid needs to see the center, the genetics folks, and you know what I mean? And so, I think that it's such a shame that it can be such a long journey for these parents. And I have so much empathy for what they're going through.

But that's why we're here, raising awareness about rare diseases. And hopefully this gets out to a lot of ears. For the listeners out there, this would be a really good one to share, just because we're going to be able to make a difference in folks' lives if they hear about rare diseases, and then kind of connect that with, well, maybe that's what's going on with my kid, and talks to their pediatrician, and maybe gets in to see genetics, and finally we figure it out.

That's the goal, right?

[Dr Beth Kozel]
I wanted to add, based on something that you said, just because it's exciting in terms of what we're able to do from sort of a research perspective, that there actually are folks here thinking about how we can use those pieces, parts, in the medical history that come in. We're starting to use electronic medical records, and everybody puts their information in the same place. And so, when I see a patient, I am doing that sort of deep dive through that thing, but that's sort of manually, and me looking at things, but how do we use some of these tools so that we can say, oh, this patient has this diagnosis and this diagnosis.

If you add up to a certain amount of points, for lack of a better word, in terms of stuff going on, do we have the ability to do kind of what I think you suggest, which is sort of put a banner in their chart that speaks to their pediatrician, or speaks to the folks that are seeing that says, this might be genetic. Could you think about getting them over there, or this could be a condition that would do that. And I think that we're starting to get to that place of being able to sort of get around those multiple visits and bring them to a single central place to say, there's something going on here.

This suggests a need to look further. And I think that's one of the places where technology is going to be able to help us in that regard.

[Dr Mike Patrick]
Yeah, absolutely. And AI sounds like it would be a good candidate for something like that. That would be incredible, really.

If you had an AI in the background of your electronic medical record, and it pops up like, hey, have you thought about this? And maybe you have, and you've ruled it out. And it doesn't necessarily mean that that's what's happening, but it just at least broadens your differential diagnosis a little bit, which can be tough when you're a busy pediatrician and trying to get through your day of seeing so many kids.

And in a perfect world, you'd be able to spend as much time as you needed thinking about each child, but that can become difficult when you're inundated with other kids that you're trying to see. So, we don't have a perfect system, but at least we have smart people working to make it better. And that's an important thing for sure.

Vidya, what are some things that we can all do to raise awareness about rare diseases and support affected families? We have a lot of listeners out there who perhaps you are not impacted by someone with a rare disease. Maybe you're hearing about this for the first time.

What can we all do to improve the lives of those who are impacted by rare diseases?

[Dr Vidya Sivaraman]
Yeah, so I think the biggest message I have is that rare is everywhere. Like, we think of it as being something that's rare, but when you put them together, it's really everywhere. And I think many of your listeners would have either a family member or a friend or somebody they know, an acquaintance that's impacted by a rare disease.

And there's different ways that you can participate. So again, like I mentioned, the website for NORD, which is the National Organization for Rare Disease, they have all kinds of fun things that you can do. And so basically showing your colors.

And they have all these neon colors that kind of come together as a symbol of rare disease. And so, it can be anything, you know, that people want to do. They can participate in any way they want by just showing their colors.

The zebra, like I said, is another logo. So just kind of showing that awareness. We actually light up, at Nationwide Children's, we have these light sticks around the corner of the hospital campus.

And they're all lit up in those neon colors during the week of Rare Disease Day. And so that's another way that we kind of highlight the importance of rare diseases. Trying to attend an event, you know, in your area would be amazing to be able to just participate and connect with others.

For patients also, I would add the component of advocacy just at a local, regional or national level. Because oftentimes, even our state representatives are not aware of these conditions and the challenges that they go through. So, legislation can be another huge part that, you know, people can play a role in.

So, reaching out with questions, you know, anything that, you know, they're interested in, whether it's that diagnostic journey, treatments, and really any way that they are able.

[Dr Mike Patrick]
Yeah, absolutely. And we are going to have a lot of links in the show notes for folks. So, we will have a link to the National Organization for Rare Disorders or NORD.

They also have a page on their site that is more information about Rare Disease Day. We have a lot of listeners throughout the United States, in all 50 states actually. And so, you know, Nationwide Children's may not be the closest center of excellence for you, but you can check out NORD's website and get a lot of information and maybe find resources that are really close to you.

Although I will say that if you are not able to find something close to you, we do take referrals from all around the country. And especially in the days of the telemedicine and phone consults, there are ways that we may be able to help you here at Nationwide Children's Hospital, even if you are in Oregon, for example. And so, we'll put a link to the genetics and genomic medicine service at Nationwide Children's Hospital and also our pediatric rheumatology program at Nationwide Children's.

And on each of those sites, there is information for contacting those services, not only for patients and families, but also for primary care providers who may have questions or want to make a referral. All that information is going to be there in the show notes. We'll also have a link to Rare Disease Day at Nationwide Children's Hospital, so you can see all the things that are going on.

And if you or your family are impacted by a rare disease, we would encourage you to register for Rare Disease Day at Nationwide Children's, which again is going to be on March 1st, 2025. And we'll put a link to the registration page in the show notes, so you can just go right over to pdacast.org, find the show notes for episode 573, that is this one, and you'll get all that information there with the links to all the things that I just mentioned. So once again, Dr. Beth Kozel and Dr. Vidya Sivaraman, pediatric rheumatologist, and Dr. Beth is a geneticist with our genetics and genomic medicine program. Thank you both so much for stopping by today.

[Dr Beth Kozel]
Thank you for having us. 

[Dr Vidya Sivaraman]
Thank you so much for this opportunity.

[Dr Mike Patrick]
We are back with just enough time to say thanks once again to all of you for taking time out of your day and making PediaCast a part of it. Really do appreciate that. Also, thanks a lot to our guests this week, Dr. Beth Kozel and Dr. Vidya Sivaraman, both with Nationwide Children's Hospital. Don't forget you can find us wherever podcasts are found. We're in the Apple and Google podcast apps, iHeartRadio, Spotify, SoundCloud, Amazon Music, YouTube, and most other podcast apps for iOS and Android. Our landing site is pdacast.org.

You'll find our entire archive of past programs there. Show notes for each of the episodes, our terms of use agreement, and the handy contact page if you would like to suggest a future topic for the program. And again, we do have more spots open up for 2025, so we're going to need your help filling those spots.

So, if there's a particular topic that we have not covered, make sure you do check out the archive. Just do a quick search, and if we've covered what you're interested in in the last couple of years, let us know if maybe there's a different angle that you would want to hear about. So, if we've already covered something with a podcast, let us know if there's something else or more that you need, and then if you don't find your topic in the last couple of years, let us know that too, and we'll try to get it back into the lineup for you.

If it's been a long time, we'll just cover it again. If it's not been that long ago, you know, we may try to find a little bit of a different take or lens to examine whatever it is that you are interested in. But whatever that is, just reach out to us at the contact page over at pdacast.org.

Reviews are also helpful wherever you get your podcasts. We always appreciate when you share your thoughts about the show. And those reviews, you know, the number of reviews that you get, and of course the quality of those reviews, really are part of the algorithm for the podcast platforms that disseminate the podcasts.

Those really do use reviews as a reason to sort of give a thumbs up or a thumbs down on particular podcasts. So, we'd appreciate your help there. We're also on social media.

We love connecting with you there. We're on Facebook, Instagram, Threads, LinkedIn, and X. Simply search for PediaCast.

You know, I've thought about Blue Sky. You know, if there's a particular platform that would be easier for you to get reminders and promos for the podcasts, let me know that as well. We haven't updated our social media platform list in quite a while, so maybe 2025 is the year to do that.

So, if there is a place where you are and we are not, please do let me know. Also, we have a couple of other podcasts I want to tell you about. PediaCast CME, of course, that is similar to this program, but we do turn the science up a couple notches and offer free category one continuing medical education credit for those who listen.

That includes physicians, nurse practitioners, physician assistants, nurses, pharmacists, psychologists, social workers, and dentists. And it's because Nationwide Children's is jointly accredited by all of those professional organizations, that's how we're able to offer these credits. And they're likely the exact credits you need to fulfill your state's continuing medical education requirements.

Again, because they are category one credits. Shows and details are available at the landing site for that program, pdacastcme.org. You can also listen wherever podcasts are found.

Simply search for PediaCast CME. You do want to make sure that the topic that you're listening to, especially if you're going to claim category one credit, you do want to make sure that the topic matches your scope of practice. But, you know, a lot of our topics over on that program are very broad.

And so, we do cover specific diseases, but we also talk about really big overarching things on that podcast as well. So, it's likely that we do offer something for everybody. We also have a podcast for faculty at academic medical centers.

It's called FAMEcast, and that's coming to you from the Center for Faculty Advancement, Mentoring, and Engagement at the Ohio State University College of Medicine. That is just kicking off this month. And so, I think it's going to be about the third week of January that we'll have our very first episode that you can find at famecast.org.

And that podcast will also be available wherever podcasts are found. Just search for FAMEcast, F-A-M-E-C-A-S-T, all one word. That is our faculty development podcast, which again is just getting kicked off this month.

I want to thank you all again for stopping by. And until next time, this is Dr. Mike saying, stay safe, stay healthy, and stay involved with your kids. So long, everybody.
 

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