Zhandong Liu

Transcript

My name is Zhandong Liu. I'm an associate professor at the Baylor College of Medicine and also the chief data scientist at the Texas Children's Hospital. I was involved in a CZI project with Hugo Bellen and Shinya Yamamoto on how to speed and accelerate the diagnosis process.

My lab focused on developing AI algorithms. I was brought in this project to kind of figure out how to use AI to speed up the process.

Our algorithms takes the genome sequencing files from a patient along with their clinical files and process it using a tool called AI‑MARRVEL and will generate a small list of candidate variants and genes that can explain the phenotypes of the patient.

These algorithms were trained on a large amount of data that's been curated through Baylor Genetics, Baylor College of Medicine, The Undiagnosed Diseases Network. As you all know, that data is AI nowadays, right? When you are talking about high quality AI algorithms, oftentimes, those were trained on very good data sets.

We happen to have access to some of the top quality data sets that's curated at Baylor College of Medicine. These are about 4.5 million variants that have been reviewed by our board‑certified clinical geneticist. And based on those data sets along with the expert knowledge that we learned by interviewing those domain experts, we were able to create this state‑of‑the‑art artificial intelligent algorithm called AI‑MARRVEL.

We have used this algorithms on a couple projects. The first one is The Undiagnosed Diseases Network project where we were doing reanalysis. The second one is a project sponsored by CZI. It's called TMC‑CZI. A lot of the children that go through Texas Children's Hospital were sequenced and our algorithms was used to help them to do primary diagnosis and then secondary analysis as well.

The third project is the one that's sponsored by NIH called the Texome Project by Hugo Bellen and the Michael Wangler, where we were helping underserved population to gain access to whole exome sequencing, whole genome sequencing platforms and enable the AI diagnosis on this small population.

So, overall, the tool has been developed for almost two years and we have seen this tool being used in many groups and enabled to identify those very difficult variants used from hundreds or thousands of mutations.

Linda Martin

Transcript

It's almost hard to believe now, but the summer of 2016 was a game changer, a life changer. Everything in my life had sort of fallen into place.

The summer of 2016 was amazing. My kids were grown, I was an empty nester. My older daughter had two beautiful boys. My son had one beautiful baby girl. My younger daughter had just gotten married a few months before. We had just sold our company and my husband and I had gone to Europe for a celebration trip.

As we had planned, he went right to Florida to our home and I went to Chicago where I was so excited to babysit my new baby granddaughter.

So, I'm in Chicago and I had just put my baby granddaughter June to sleep, came downstairs to relax after the trip. I was a little bit jetlagged and the phone rang. It was my husband calling.

I was like, “Hi. It's great to hear from you. I'm having so much fun.”

And he said, “We have a problem.”

I was like, “How could we have a problem? We just got back from vacation. We couldn't possibly have any problems yet.”

He said, “Well, I just had coffee with Kim and Kim said that she had gone to the doctor with Amy.” Amy is our younger daughter. She had just gotten married, as I said, a few months before. Was doing great.

Amy was sick, so Kim had accompanied her to the doctor and came back. Amy had said, “Don't tell Mom. Don't tell Mom.”

True to her word, Kim did not tell Mom. Kim told Dad.

So Dad was calling me to say, “I've got some bad news.”

But we didn't even know what the bad news was yet. All we knew was that Kim said, “Dad, I went to the doctor with Amy. She has something called chronic pancreatitis, but that's not what I'm worried about. Dad, Amy is dying.”

I was just speechless. How could this happen? I had just seen her a few weeks before.

Then I thought about it. I had not seen her a few weeks before. I hadn't seen Amy for a few months. She had gotten married, she had gone on her honeymoon. She and her husband were busy and happy. I hadn't seen her for a few months, but, as far as I knew, she was fine.

And, suddenly, I'm back from vacation, I'm babysitting my granddaughter and she's dying? And what is chronic pancreatitis? I never heard of it. None of us had ever heard of it.

So, I said, “Well, we have to do something.”

My husband said, “Obviously, that's why I'm calling you. You are the someone who does things.”

And I said, “Yeah, but I don't know what this is.”

So, we hung up and agreed that the next day we would talk again when we could make some more sense of it and I could talk to Amy and reveal that her sister had told us what was going on.

And so I hung up the phone and I did what every mother does when she has no idea what's going on with her kids but she knows enough to be worried, sat down on the floor and I Googled.

I Googled chronic pancreatitis. What was it? How could she be dying? I found out that she might not be dying, but chronic pancreatitis was associated most commonly with alcohol abuse.

I kept reading article after article after article about alcohol causes pancreatitis and then pancreatitis evolves into chronic pancreatitis only in some unlucky people. Apparently, my daughter was one of those unlucky people.

I thought, “Well, I think I saw her have a glass of wine at her wedding,” and I know she occasionally has drinks. She's 40 years old. She's had a drink before, but she's not an alcoholic. She has never abused alcohol. This just didn't make any sense to me whatsoever.

I didn't sleep at all that night. I did a lot of Googling. I thought, “I just don't get it. I just need more answers. I need to find out who's an expert in this sort of thing.”

The next day, of course, I talked to Amy and my daughter Kim. Amy said, “I don't know. I've just been really sick, Mom. I've been so sick I just didn't want to tell you because you were so happy. You were going on vacation and I knew you were babysitting. I thought there's time. When you get home, I'll tell you that I haven't really been feeling very well.

But then Kim convinced me to go to the doctor and my doctor gave me a referral to a GI. We went to the GI. She took some scans and then she said, ‘You've got a big problem. You have what I think is chronic pancreatitis and you've had this for a really long time.’”

And Amy said, “So I said, ‘So what do I do,’ and the doctor said, ‘Just stop drinking.’”

And my daughter Kim said, “That's exactly what she said, Mom, and she said it even meaner than that. So we left and we were in tears and we didn't know what to do. And so chronic pancreatitis, and we need to do something.”

I said, “Okay. We're going to figure this out. There are people that know what this is all about. There are doctors who are specialists. We're going to find them, we're going to take you to them. I just don't know what to tell you. But, Amy, have you been drinking a lot?”

She said, “Mom, yeah, I drink occasionally. I have a glass of wine occasionally. You know I don't drink that much.” And she said, “I was so mad at the doctor. I said, ‘But I don't drink,” and she said, ‘Don't lie to me, young lady. Just stop drinking.’”

I said, “Okay, okay. We're going to figure this out.”

I was in complete stupor. I didn't know what to do. I kept Googling, I kept looking for where are the experts and it seemed like there were none. Where was the research going on? There was none. Where was there drug development going on? There was nothing. There was just article after article that said, “Alcohol causes pancreatitis and pancreatitis leads to chronic pancreatitis, which leads to diabetes and, eventually, to pancreatic cancer. There's a lot of pain involved and it's a debilitating disease that's progressive. There's no cure and there's no treatment. There's nothing you can do.”

So, we said, “Okay, this is who I am. I fix things. It's like there's a problem here. We have to solve the problem. We just have to find the people.”

So in my Googling, I had found a press release from a woman who said, “I think I'm going to start a nonprofit organization called Mission: Cure to find a treatment for pancreatitis. My brother has chronic pancreatitis. There are no treatments. There's no cures. We need to do something and I'm going to start a nonprofit.”

So, I got in touch with her and said, “I'm coming to New York to meet you.”

And I sat down with Megan Golden, who was thinking about starting an nonprofit, Mission: Cure and said, “I need to do this with you. I just sold my company. Nobody's doing anything. We have to do something. We have to find a solution for this.”

In the meantime, my daughter is getting sicker and sicker and sicker. She's in the hospital every few days and then maybe a week goes by, back in the hospital, back in the ER. They give her fluids, they give her pain meds and they send her home, say, “There's nothing we can do.”

So, we just continued down this path, trying to find somebody who is learning something, doing something, and, eventually, got in touch with a couple of doctors that were working on pancreatitis.

Eventually, I learned that the University of Minnesota in Minneapolis is the one institution in the entire world that treats chronic pancreatitis and had perfected a procedure called a total pancreatectomy with islet transplant that was a huge surgery to remove the pancreas and four other organs. It was the only treatment, and is today, for pancreatitis. There are still no drugs, no treatments, very little drug development pipeline, a little bit more research after the last seven years of Mission: Cure, but still no real treatments.

But my daughter was getting sicker and sicker. Amy was in the hospital, eventually went into sepsis. The doctor in the hospital said, “Do you know any place that knows any more about this disease, because there's nothing else we can do to help you? I want to just discharge you and you can go find someplace that can treat you better.”

Amy called me from the hospital and said, “Mom, I'm being discharged.”

I was like, “Oh, Amy, that's great news.”

She said, “No, Mom. They said I'm in sepsis. There's nothing they can do for me and they want me to go find someplace else.”

So I went and picked up Amy, we flew to Minneapolis and she got a full assessment there. Together, we sort of just wandered through a jungle of information that we had no idea what it was about, but eventually decided that this tremendous surgery was the only possible solution for what had become 24x7 nonstop pain.

In the ensuing time, Amy had lost tremendous amount of weight, was surviving on little boost cans of protein drink. It was the only thing she could keep down. And she had no life. She had previously run a software company and had to go on disability, quit working because she was in bed, in pain 24/7, and losing weight and, as my other daughter said, about to die.

So she made this terrible decision that was to have these four organs removed in this total pancreatectomy solution.

In November of 2018, finally the surgery gets scheduled. Amy has the surgery and, ta‑da, no pain. She can eat anything she wants., It was a very long recovery, but life was back. Amy had a life again.

All of that is just amazing. It's like the highs and the lows. She's dying. No, she's not dying. I'm going to have to live with a disability all my life. No, I'm actually going to have to go find a job again. And how do I as a mom support all of these roller coasters of things going on in my daughter's life?

In the meantime, her husband left. Amy is all by herself now. So, we make it through all these things. And while chronic pancreatitis is not a death sentence, people don't generally die from it, it robs you of your entire life.

But Amy had this surgery, a surgery that's full of risk, left her as a fully diabetic and taking enzymes with every bite of food for the rest of her life, because the pancreas does two things: it makes insulin and it makes digestive enzymes. Without a pancreas, you need to do both externally, which she was doing.

But she was getting her life back, went back to work, when, suddenly, the complications started coming in. And because of years and years of misdiagnosis and a very long journey until she was finally diagnosed, she had had so much inflammation that she had robbed her bones of blood supply and had had to have two hip replacements, followed by complete and total kidney failure and is now back on disability and going back in to try to correct some of the scar tissue and other problems. Now, she's back into complete lack of ability to keep down food, vomiting back in the hospital, off and on, over and over again.

This story is one that has so many highs and so many lows. Through the last seven years, my daughter has gone through what seemed to be a cure, at least a treatment that took away chronic pancreatitis. She does not have chronic pancreatitis. She doesn't have a pancreas so she can't have pancreatitis. But it isn't a real solution.

We so need therapies. We so need to find pharmacological solutions so that children and adults who get pancreatitis don't have to go through this life‑changing surgery that is not a panacea, and shouldn't have to continue to live with the suffering, the digestive issues and the terrible pain with the only solution to go through this 15‑hour under general anesthesia surgery that doesn't end in Happily Ever After but just in some different manifestations and complications that Amy will have to deal with the rest of her life.

Thank you.

Gareth Baynam

Transcript

I'd love to share with you a story, a story about a gift, a gift that keeps on giving, a gift from one of the most remote places in the world, in the western desert of Western Australia, a gift, a gift from three remarkable Aboriginal children, who each in turn were born with a devastating condition, a condition affecting their hearts, their brains, their breathing, their learning. They then ultimately went on to develop intellectual disability and seizures. A gift that transverses time and transverses our planet.

These three children unlocked incredible medical insights. They were discovered to have a rare condition, a glitch into a change in a single chemical in a single gene, a gene called MTOR. This change made the gene work way too much. It was overactive and that caused chaos throughout their bodies.

When we first found this gene change, there was no map. There was no map to compare this gene change against for Aboriginal people, to know whether or not this was an abnormal gene change.

So then we had to go on a remarkable journey. We searched all over the world to find people that could prove whether or not this gene change was in fact the cause of these children's condition.

After circling the world, we kind of landed in our backyard. We landed on our own country with an immunology lab. They proved that that gene in fact did work far too much in experiments in cells in the laboratory. But much more importantly, they also showed that if we gave a commonly used medicine, a cheap medicine with a known side effect profile, that we could reverse the effect of that faulty gene in those cells.

Suddenly, we not only knew definitively what the cause of this children's condition was but we immediately had an option for their treatment using an existing drug, something we could take off the shelf. We didn't need to go through a billion dollars and 20 years of drug development. We could use that right now.

This condition ultimately came to be known as Smith‑Kingsmore Syndrome.

With the permission of the family, we published this information to see if there are other families around the world. And then a chain reaction of events occurred as others were diagnosed around the world, a bit like cousins around the world for these Aboriginal children.

Then there were new insights. In Germany, two siblings were identified with the condition, teenagers. And they had bowel polyps. That's very unusual in teenagers. Bowel polyps are the precursor of bowel cancer.

So, suddenly, we didn't potentially only have a treatment for seizures, intellectual disability, but also potentially bowel cancer. Again, something that was off the shelf.

Not only does this gift give internationally, it gave locally to our community in Western Australia. We solved this medical mystery using genomic sequencing back in 2013. It was the first time we had used that as a clinical test. That then gave our health system and it gave the Aboriginal communities the trust and the confidence to be able to do that more. It set up our Rare and Undiagnosed Diseases Diagnostic Service and, ultimately, what became the Undiagnosed Diseases Program.

The gift keeps on giving, because that Aboriginal family taught us how to provide the best medical care, how to embrace Aboriginal ways of knowing, being and belonging to help everybody.

We then took those principles to design how we provided care coordination for people with rare and undiagnosed diseases, care coordination across all of what it means to live a life in children, be it health, education, disability and social services.

So, to that Aboriginal family, to those three children, those incredible, vulnerable, special, powerful children from one of the remotest corners of the earth.

Thank you.

Leah Myers

TRANSCRIPT

Ben's story starts out like a dream, the kind of fairytale that every parent hopes for. He's born on a Friday, weighing 8 pounds, 9 ounces. The moment I lay eyes on him, I know I have never seen anything so perfect in my entire life. I swear, he's the prettiest baby in the nursery and that's a fact, not my bias.

The first morning after he's born, I'm just too excited to wait for help. I get myself out of bed and I dress Ben up in the softest baby blue sleeper that I had packed with so much anticipation. Seeing him in that little baby sleeper just made my heart want to burst with pride and love.

I had waited for that moment for 20 weeks ever since we had learned that he was a boy on the sono. I don't need to wait anymore or imagine. My baby is here and I am a mom. That feeling of holding your child for the first time, of looking down and thinking, “I did this. I created this life,” is overwhelming.

As a kid, I'm always the neighborhood babysitter, always pretending to be a mom. Caring for kids is a huge part of who I am. I imagine, one day, I'll have a family of my own and it'll be big, a whole gang of kids running around. Everyone that knows me doesn't doubt that's my destiny.

But as my 20s roll into my 30s, the dream of a large family starts to slip away. At 34, I finally get those two pink lines on the test. My dream is coming true. But because of my age, my pregnancy is deemed high risk, but I couldn't care less. None of that matters to me.

I figured this might be my only chance so I'm going to cherish every single second of it. Every flutter, every kick, every movement feels like magic. I'm literally glowing, the happiest pregnant woman you could find. I've waited so long and now, finally, it is happening.

The first few months after Ben is born are a blur of joy and exhaustion, as it is for any new parent. I'm mesmerized by every little thing that he does. But underneath that joy, I have this gnawing feeling that I just can't shake. I keep telling myself that all babies are different, but something about Ben is, I don't know. It's off.

My mom friends brush off my concerns, tell me it's hormones or first‑time mom and not to worry. And Ben is an easy baby. Super laid-back, very mellow. He barely cries. But there are moments when I look at him that I see something that feels wrong. He seems too flat, too disengaged at times. He won't nurse, although I try everything.

He won't make eye contact with me, and that's probably the hardest part because I've dreamed of those intense bonding moments where you're feeding your baby and you lock eyes and the whole world melts away. I want that so badly, but it doesn't come.

I start to think, “Maybe I should blame myself. Maybe I'm doing something wrong.” But, deep down, I know Ben isn't like the other kids that I've cared for in my past and that really scares me.

I try to voice my concerns to his pediatrician, and every single time I'm dismissed. I hear it all. “You're a paranoid first‑time mom. He's a boy and boys are lazy.” Which isn't untrue, right?

But just before he turns one, the changes become undeniable. He stops smiling. He loses the few sounds that he was making, which were ‘Mama’ and ‘Dada’. I feel like I'm watching my baby slip away.

My husband and I are sure it's autism and we try to brace ourselves for that reality, but, still, I find myself clinging to hope. I want to believe that Ben will be okay, that he's going to be the kid that I dreamed of and that he's still in there somewhere waiting to come out.

At Ben's one‑year checkup, we stand strong. We stand our ground and we demand to be heard, insisting that something is wrong. We're finally referred for developmental and hearing tests, but six days later, Ben starts to have seizures.

At first, I don't even recognize these as seizures. They don't look like what I had imagined. No convulsions, no dramatic movements. Just these quick, aggressive head drops that happen over and over and over again in clusters, one every six seconds. On bad days, these clusters lasted up to an hour. It's terrifying, but because we're so fixated on the idea of autism, it doesn't occur to us that this could be medical.

Thankfully, I've been persistent with our pediatrician. So, when I call to report it, she says, “Get to the neurologist really quickly.”

Suddenly, we're plunged into a world we don't understand. Conversations about brain disorders, terrifying diseases, even end‑of‑life care. It all feels surreal. Like, how did we just go from me trying to convince the doctor something was wrong to having a seriously sick baby? It all escalates so fast.

Within a few weeks, we learned the truth. Ben has a type of epilepsy called infantile spasms. The first thing that comes up when I Google it is an article titled “Little Seizures, Big Consequences.”

I'll never forget reading those words and feeling like my world is collapsing around me. The prognosis is grim. 90% of babies with infantile spasms either don't survive childhood or go on to living an extremely disabled life.

But I grab on to the only hope I can find in there, that 10% chance that we can still be one of the lucky ones and I tell myself we're going to do everything we can to fight our way into that 10%.

The first treatment is a brutal round of steroids, the kind of dose that you'd give to an adult. Ben's little body doesn't handle it well. He swells up, his sweet face red and puffed. He loses every single milestone he had gained in his first year. He can't even hold his head up anymore.

But when I call his doctors desperate for reassurance, they tell me to keep going, so I do. I force that drug down his throat four times a day, hoping it will work, praying it will stop his seizures, but it doesn't. Neither does the next drug or the next or the next.

Each time we start a new medication, I let myself hope again. I picture Ben's future, imagine him laughing, running, maybe playing Little League one day.

Then one day during a new round of treatments, Ben goes an entire day without having a seizure. My husband and I, we hold our breath, not wanting to get too, too excited, but that night we let ourselves dream again. We talk about what sport Ben might like, what it would be like to see him in that Little League uniform. I can picture it so clearly, a bat in his hand, grinning from ear to ear.

But at 2:00 AM we're jolted awake by the sound of Ben's head hitting the crib rails as another seizure hits. Crash! It's like the sound of hope shattering.

This goes on for months. Each new drug, each new glimmer of hope, followed by another crash, another heartbreak. I hold on to the belief that we have to be one of the lucky ones.

After months of searching for answers, we seek a third opinion in New York City. This doctor admits us right away and we spend eight long days in the pediatric ward at NYU Langone Medical Center.

I will never forget how small that room feels, crammed with machines monitoring my baby's brainwaves. He's hooked to wires. There's a camera always watching us. There's no privacy, no peace. I sleep on this crappy, blue pleather chair next to his hospital crib.

Ben is hooked up to everything. I have to jab him in his thigh with injections twice a day and he barely cries. Neither do I. I hate it. I hate every moment, but I cling on to the hope that this will be the treatment that works.

Then, miraculously it does. Ben’s seizures begin to slow and then, after five days, they stop all together.

We're ecstatic. And at our follow‑up EEG, the doctors are just as thrilled as we are. They said that they see major Improvement on his EEG.

I allow myself to believe that we're finally in the clear. Ben's going to be okay. We are the lucky ones.

As we prepared to leave the hospital, I called my sister to share the good news. And while I'm on the phone with her, I turn around just in time to catch Ben having a major seizure.

I drop the phone, hit the nurse call button and I start screaming for help.

The next 45 minutes is a blur. I remember holding Ben as he continues to seize. The clinical team comes in. They get me to sit down in that hateful blue chair. They shove a pillow under Ben's head so it won't hit the armrest on the chair as it violently drops over and over and over again.

I'm hysterical, completely opposite of the hopeful composure I've been able to keep up with since diagnosis. The tears flow steadily as I unleash the pain, as I've not yet let myself grieve. I start to cry that I'm going to lose my job, that Ben will never play in Little League. I'll never be able to have another baby, killing my dream of a large family.

I'm completely disoriented by the swing from elation to devastation. It's like the rug was pulled out from under my feet, leaving me emotionally freefalling, just trying to make sense of this abrupt shift.

The team just sits and listens and monitors Ben. They don't even try to tell me it's going to be okay.

My husband walks in somewhere in the middle of this. He has no idea what had just happened and he has this profound look of helplessness on his face, yet I'm incapable of comforting him as I'm still in crisis myself.

As Ben's seizure begins to slow and eventually stops, so do my tears. I'm utterly exhausted and barely able to function. Somehow, we managed to pack our bags, go through the discharge process and load up into the car to drive the five hours home.

I sit in the back seat with Ben and I stare at him. He sleeps most of the way, being post‑Dicel and snowed on drugs to stop his seizures, and he seems different to me somehow, almost like a different baby.

I'm tortured with the guilt of feeling that this is not the kid that I had planned for, that I had dreamed of. That baby is gone and I'm going to have to figure out how to parent this beautiful boy an entirely different way than I had ever planned.

We were so close to being one of the lucky ones.

Thank you.

Katie Stevens

TRANSCRIPT

12 years ago, my day‑to‑day worries included things like, did the kids make it to school on time? For the first time ever, all three of my kids were in school. Did the laundry get done? Did I get up at 5:00 AM for my six‑mile run?

I remember telling my friend this was going to be the year that I get some rest and I figure out who I am. I'd been a mother since I was 18 years old and I was excited to think about going back to school.

My oldest, Riley, was born a perfectly healthy little boy. He grew into a very strong 11‑year‑old who is running 5Ks alongside me. That summer, we started to notice some abnormal bruising. Things like seatbelts would leave marks across his neck. His friends who played soccer, their legs looked fine, but Riley's were littered with bruises.

We took Riley to his annual visit in August and his pediatrician assured me that it was okay to wait for lab tests and that we didn't have a history of cancer in our family, so it was okay. Things were going to be okay. He scheduled labs to be drawn in October.

Over the next few weeks, we started to notice little things, like a cough that just wouldn't go away or, when he went for a run with his Dad, he said he just felt really tired. My gut was telling me there was something to be worried about, but I brushed it aside because his doctor said it was okay. What did I know? I was just a mom.

The night before his blood draw, we watched a St. Jude's commercial. I looked at my husband and I said, “I think something's really wrong with Riley.”

We pulled up to the lab and I prepped Riley. It was just going to be one poke. I would hold his hand and we’d go get one of those $1.50 hotdogs from Costco.

They drew 14 vials of blood. We got home that afternoon and Riley went outside with the kids to play. And he ran in and asked something. His face was sweaty, his hair was sweaty but he was smiling, but he was blue.

I put my ear to his chest to make sure he was breathing okay, because I thought for sure that was it. Little did I know, those 14 vials of blood had drained him of the already dwindling blood supply.

I called his doctor. He told me to get Riley to the ER. I didn't know then that he had already seen the results of Riley's blood draw.

The ER drew labs again. They looked at me and said, “You need to get him in the car. You need to get him over to the next state,” which was Washington, into the children's hospital because my rural Idaho hospital couldn't handle what was happening to him.

The doctor at the children's hospital pulled my husband and I into a tiny room away from Riley and told us the devastating news that our child who had been hiking mountains over the summer either was in bone marrow failure or had cancer. His body was no longer equipped to sustain life.

Less than 12 hours since we were eating a hotdog at Costco, we were admitted to the hematology‑oncology floor.

As we got settled in for the night, I was tucking him into his hospital bed. How had I not noticed how pale he had become? His white skin matched the sheets and the hospital lighting and all I could see were his blue eyes that were full of fear.

“Please sleep with me in bed tonight, Mama. I'm really scared.”

My only worry now was that I needed to save my child's life.

The next morning, my husband came and I asked if I could step into the hallway. I covered my mouth and I sobbed and I shook and I broke. I couldn't let him see me like this. I couldn't make it so scary. How was I going to hide that I knew he could die?

Riley was diagnosed with severe aplastic anemia, a rare bone marrow failure disorder. The cause was unknown, but our family history, again, didn't make anyone think it could be genetic.

Riley had had two options at survival. Two. One was an immunosuppressive therapy that should train his body to quit attacking itself. The trick, he couldn't have an underlying genetic condition for it to work.

The second was a stem cell transplant. It was much more dangerous and his best chance at life would be if he had a sibling match. The problem, neither one of our children was a match for him.

So, because there was no known genetic issue, because testing hadn't been run, and he didn't have a sibling match, immunosuppressive therapy was ordered to start on Halloween.

Here's the thing. My deep knowing knew we were going to be headed to stem cell transplant if this didn't work. And my deep knowing knew that my thriving child didn't go from perfectly healthy to dying. That just doesn't happen.

My life was so different from where it was three weeks prior. I was still worried about laundry, but this time I was delegating it to whoever was able to help us at the time. I was coordinating hospital dinners with my family just to try to keep some sense of normalcy.

I was fighting insurance companies and I was fundraising just to make ends meet and to make sure my littles could stay in swim lessons.

16 weeks would have to go by before telomere length was performed and showed that Riley did have a genetic condition. Remember the immunosuppressive therapy? Well, it was a fucking nightmare to watch him go through and it was never going to work.

Telomeres. This was a word that had never crossed my lips. My 11‑year‑old knew it from middle school biology and I started realizing right then and there it was up to me to understand all the nuances of the science that was happening inside of him and the treatment available to him, because you know what? Doctors have a lot of patients, but I only had one Riley.

Telomeres were the word that changed my universe. They're the protective end cap of our DNA and they work like the aglet of a shoelace. They keep our DNA from unraveling. When we're born, ideally, they're longer. And as we age, they shorten. Riley’s are what you would expect in an 80 to 90‑year‑old person.

In the midst of all this, we're trying to find resources. One co‑pay was $800 a month. Our case manager was amazing and he tried to prepare me. He said, “You're going to be in this ocean of cancer and aplastic anemia is this little, tiny island.” And now we had the diagnosis of telomeres and we were on a rock, stranded. Alone.

This was the dance I found myself in for the rest of Riley's journey. Patients with short telomeres can't have a standard stem cell transplant protocol. Alkylating chemos and radiation destroy them, and the data showed there was very few that survived it.

They told us that Riley had a donor identified, a 23‑year‑old male who wasn't answering the phone. To me, the most logical thing to do was to tell them to call his mom.

In this time of sheer chaos, Riley's body was somehow giving us time to find the right path. We were connected to the patient advocacy group via Facebook and they were hosting a camp in Maine, where experts from around the world would be and other families like ours would be there as well. We went and we were welcomed with open arms. We were no longer alone.

We met a doctor who had designed a protocol, stem cell transplant, for patients with short telomeres. The clinical trial already had patients that had gone through it and it showed that they were doing very well.

Coming home, I was so excited to tell our hematologist what I had learned. Riley met all the criteria for this clinical trial. We knew it was a risk, but all transplants are a risk and I wanted to spare him the complications that I knew he would endure due to his genetic condition.

He looked at me and smiled. I think we're just going to stay with the plan.

Riley doesn't show the typical signs of someone with a telomere issue. This time, though, I wasn't going to listen just because they told me to. This time, my gut told me that this was the treatment that was right for Riley.

I moved Riley 3,000 miles from home. I left behind my other children and my husband. Riley was number six in the world to undergo this clinical trial. We Life Flighted the now 24‑year‑old’s marrow from Germany. He picked up the phone.

Riley's body accepted his cells as his own and, now, nine years later, we have never been back in a hospital in all that time.

A year later, we were back to status quo, but for me it was too quiet. To my surprise, I had found out about myself. Through this process, I learned that I really understood and enjoyed the complexities of genetics. Helping people that were on that rock felt like it was my calling. I was asked not to just help but to step into the role as the first executive director of the leading international research and advocacy patient organization for telomere biology disorders.

Today, I worry if someone has received proper diagnostic testing, if a clinical trial is developed in an equitable and accessible way. I worry about grants and fundraisers and sell lines. I worry if Riley and Olivia are doing okay in college. I worry if Ethan is enjoying his senior year. Oh, yeah, I had another baby during this. Grayson is 11 and he knows what telomeres are too.

Some things never change. I still need to do the laundry, I still need to run, and Costco hotdogs are still $1.50.

Thank you.

Alison Peck

TRANSCRIPT

About 10 years ago, my family moved back to my hometown in South Georgia. I didn't really want to go back to my hometown, but that's a different story.

My husband, Nathan, had taken a job in my small South Georgia town. It was our seventh interstate move in nine years. Every opportunity he had, he took. We were ambitious.

It was a fall day. We were playing in the front yard with my kids. They were nine, six and three. I had taken a break from my career to manage the moves and to manage those kids.

In this moment, I was picking up pine cones. The kids are playing with my husband. I take a break. I was enjoying the laughter, the kicking of the balls and picking up my pine cones, but I saw something that I didn't really want to see. I pretended like it wasn't there.

My husband kicks a ball and he and my three‑year‑old run after it. The three‑year‑old beats him. He was ecstatic he beat Daddy.

My heart sank. Nathan looked at me and said, “I feel like I'm running through mud.” My strong, 30‑year‑old husband outbeat by a three‑year‑old. It was the day when we had to face that reality we'd been running from.

We went to put the kids in bed that night and we pull out this manila envelope labeled IBMPFD, inclusion body myopathy, Paget disease of the bone, frontotemporal dementia. That alphabet soup of letters that we never could really remember. We pull out a newsletter that we'd received years ago. There was this picture of scientists smiling on the front. They had discovered the gene, the family curse.

You see, his family had participated in research years ago. His mom, his aunt, his uncle and his uncle, all perfect in their childhood, no problems. In their mid‑30s or 40s, they started having trouble walking.

So we look at it and we see that gene, VCP, valosin‑containing protein. His mom had lost the use of her hands. She couldn't hold her grandchildren. Were we ready to find out? It would kill her. That was her thing. She was holding onto hope that she didn't pass on this gene to her kids or her grandkids, so we folded it and put it away.

A couple months later after she passed away, Nathan pulls it out. “I'm ready to find out.” He emails the geneticist. “Hey, can you test me for the VCP gene?”

She mailed him a kit, a blood test. He mailed it back.

We get that call two months later. It was evening. He walked from the kitchen to the bedroom. I followed him, waiting. It was a short phone call. He nodded his head. “Okay, okay.” He hung up the phone.

“I have it. I've been waiting.”

“Okay. I'm going to be the supportive spouse. What are we going to do? Who are we going to tell?”

“We're going to tell no one.”

“What? No one?”

“We're fixers. We solve problems.”

“You're not going to fix it?”

“No. This is my body. It's happening to me. And what good would telling people about my disease do? Nobody can do anything.”

He slept like a baby that night. I went into the closet and cried.

We face problems. We fix things. Here, faced with the biggest thing that we’d ever faced and we're not going to fix it? Not only that, it's autosomal dominant so it could pass to my kids.

We woke up the next morning and he went to work. I put a smile on my face.

I kept his secret for two years. How could we tell our kids if we weren't okay with it? That limp that he walked with, that was an old sports injury. The family trip, the family Cub Scout camping trip, he couldn't go because he was afraid to hike the half mile from the parking lot to the campsite. So, I took the three kids by myself, pitched the tent, cooked food over the open campfire and it was good, but I had this nagging feeling in my heart that Nathan wanted to be there and there was nothing I could do about it.

About two years later almost to the day, we get an email from the geneticist. She had found a VCP inhibitor that could potentially work for his gene mutation. This world of a researcher reaching out to us? It was crazy. People were working on this?

We called a friend. Her name was Alice. She had some weird kiddos and she said, “Alison, you need to start a patient advocacy organization.”

“What's that?”

“Well, you know, you fund research, you organize patients.”

“Oh, that sounds like a lot of work. I can't do that. I'm busy.”

“Oh, no. You can, and you will. Because if you don't advocate for your disease, nobody else will.”

So, I look back at me in my closet with my heart walled off, not being able to function, and now, there's a way to fix it. Or maybe not even fix it, but maybe take a step in the right direction. At least I have a path. It's not a straight path. It's not an easy path, but at least it's a path.

And at least when I look at my kids and tuck them in at night, they look at me and say, “Am I going to inherit my father's disease?” I can say, “Not if I have anything to do about it.”

Thank you.

Amy Wood

TRANSCRIPT

May 21st, 2015. It was a Thursday before Memorial Day Weekend. It started just like any other day. My four‑year‑old Alex got up and he was ready for his day, very excited because it's Thursday. It was Library Day at his pre‑K. It's his favorite day of the week.

I was getting my coffee, trying to get ready for the day, watching him do his morning thing, running around, watching TV, all of that stuff when I noticed something was odd about his left eye. It was crossing inward.

“That's weird,” I thought. I thought maybe he developed lazy eye. It was a common thing in my family. I had it. My mom had it. So, I took him off to school and I called an eye doctor and made an appointment then went about my day.

I was at my desk. I was a web designer at the time, so I was at my computer pretty much all day and I got an email from his teacher.

She said, “Have you noticed Alex's eye?”

I replied, “Yes. I made an eye doctor appointment.”

And she replied, “Okay.”

About an hour later, she sent me another message and she said, “I think something is wrong with the way he is walking. His balance seems off. He had trouble getting to the trash to get rid of his lunch.”

And I was like, “That seems weird.”

So, I made a pediatrician appointment. I picked him up from school and we headed over to the pediatrician's office.

The pediatrician was new. Alex hadn't seen him before. He was a young guy. He comes in and he asked Alex to walk in a straight line. He looks at his eye and he turns to me and he says, “I need you to go and take him to John's Hopkins to get an MRI. I think it's a brain tumor or brain cancer.”

I can only describe this as an out‑of‑body experience. It was like I was looking at the room from a different place. I couldn't believe that that's what he actually said.

He called in Alex's regular pediatrician. She was with another patient. She confirmed that he might be right and that we should get there right away.

Alex looked at me during all of this and he says, “Hey, Mommy, am I going to get dinner?”

And I said, “Yes, we're going to get you dinner,” as I packed him up to leave the office. I remember walking out of the pediatrician office and it was very quiet. The staff had pretty much stopped what they were doing and watched us leave. It almost felt like walking the plank.

I called my husband Sean and told him this news, picked him up and we made the two‑and‑a-half hour drive to Baltimore, which was a very anguished drive, to say the least.

When we got there, they brought him into the emergency room and started to do the vitals, which, little did I know, would be one of about a million times I'll be holding his arm still for blood pressure.

The tech whispers into my ear. She said, “Does he know?”

And I said, “Know what?”

And she said, “About the brain tumor?”

I was like, “There's no brain tumor. This is crazy.”

So, we go into the ER room and the nurses and doctors start coming in to prepare us for this MRI. They tell me he has to stay very still. He can't move. Needless to say, both four‑year‑old Alex and Mom were very scared.

We got into the MRI and I'm trying to tell him to hold still. He's scared and it's loud. He's crying and I'm crying. You know, for 30 minutes, it was pretty, pretty rough.

They got us out and back into the ER room and we waited.

A few minutes pass by, then maybe about 15, an attending walks in. She's putting on her coat and she says, “I'm leaving for the day, but, hey, they found something, so someone will be in to talk with you shortly,” and she left.

I remember looking at Sean and his face turned white. He's like, “What did she just say?”

And I said, “I don't know. I think that she said they found something.”

Another doctor had been passing by and overheard this, and she came in and took us into a room. She told us that there was a mass in the middle of his brain and that the doctors were working to figure out what they were going to do. They would be in to talk with us.

I remember Sean saying, “Is he going to die?”

And she said, “No, I don't think that's… I think it's going to be okay.”

I can describe this feeling, because I now feel it often, but it's just this like tightening of the chest and my stomach starting to hurt. It was just this like white hot fear. What is this? What is happening?

They took us to the pediatric ICU and put us in a room there. A nurse sat with us through the night as we waited to find out what the plans were and what they were going to do next.

Alex said to me during that time, he said, “Mommy, am I sick?”

And I said, “I think they're just trying to fix your eye, buddy.”

The next morning, early, in comes the anesthesiologist to tell us they were going to put him under for this next MRI. A neurosurgeon came in and said they were going to look and see what was going on so that they can decide how to treat the tumor.

They start to put him to sleep and they take him out of the room and they tell us that we can go get a coffee. So we started to navigate the labyrinth which is John's Hopkins to get to the cafeteria.

No sooner do we get there but our phones start blowing up. They call us back. “Come back right away.”

So we run back to the ICU where we meet a neurosurgeon. He tells us, “Here's some forms to fill out. We need to go into surgery right away.”

They escort us to the waiting room and we wait for eight hours. And during those eight hours, nurses came in to check on us and assure us that he is in the best hands and that everything was going to be okay. One nurse even said, “He probably will be home next week,” so we felt very reassured.

As the day progressed and we waited, the neurosurgeon came out to tell us he was finished with the surgery. He told us the tumor came out all in one lump and that it came out easily and that he thinks it's benign. So we were like, “Oh, thank goodness. “ Benign sounded not too bad, so we felt very hopeful.

They took us back into the ICU and they brought Alex out of surgery and they told us he would be awake probably within the hour, but he didn't wake up. He was covered with IVs and all these machines. And I remember the doctors coming in and jostling him and yelling at him and he didn't wake up.

So, throughout that night after surgery, there started to seem some things were concerning. One, that he didn't wake up, but, two, fluids kept leaving his body. He was just peeing nonstop.

The next morning, we were greeted with just a parade of specialists: endocrinology, neurology, neurosurgery, ophthalmology. The biggest thing they told us was that he had this condition called diabetes insipidus. Not the regular diabetes that we know about but this one that means that he doesn't make the hormone to keep the fluids in his body, and that his body will just rid all the fluids unless they give them a medication to replace the hormone.

Okay. This seemed manageable.

Until they said, “Well, his blood sodium keeps swinging. It's getting high and getting low, because we can't get the medication right.”

So, this became what kept him in the hospital for six weeks.

As we were starting to hear some different things, I heard that the name of the tumor was cranio‑something. So, I Google searched cranio brain tumor and come to find out this tumor, benign and non‑cancerous, causes the following issues besides diabetes insipidus. Endocrine dysfunction, adrenal insufficiency, growth hormone deficiency, loss of short‑term memory, neurocognitive effects, and the kicker was morbid obesity not manageable with diet or exercise and an insatiable hunger that cannot be cured by eating a typical meal.

So, all of these things we were not told about, but the one diabetes insipidus was the one where he had to be in and out of labs constantly.

After discharge, he was flown back to Hopkins multiple times. These conditions have been very difficult to manage. I learned quickly that no one really knew what was going on in the brain and how this all worked.

So, we left the hospital, and Alex was so different. He wasn't even the same kid when he went in. We were crushing medications and seven or eight different pills getting crushed up every day. And there was this constant management of care of these medical conditions that were a matter of life and death.

Ten years later, after we have learned to become his biggest advocate, and even starting a patient advocacy organization for this benign tumor, craniopharyngioma. Alex was hospitalized for septic shock just three weeks ago. He almost died. It has been ten years of battling the aftermath of this tumor craniopharyngioma, but we will continue to do so and advocate for him and all of those who suffer from this benign brain tumor.

Kim McClellan

TRANSCRIPT

One thing I'm often told by others is how strong I am and how well I handle my diagnosis of recurrent respiratory papillomatosis. But what they don't know is that I'm not strong. There are nights I lie awake, wondering if tomorrow is the day I find out I have cancer. The nights I lay awake because a young mom is called because her child had been diagnosed. So, I'm not strong, I'm not strong at all. I don't have a choice.

I was diagnosed when I was five, so this is all I know, which sometimes I think is good. But other times I think it's bad because I think I'll always wonder what if. What if I hadn’t had to worry about surgeries or my voice or the financial implications of what a rare disease brings. How would my life had been different?

So, just to let you know, I'm not strong.

Growing up, you're in the OR every week, every two weeks. So, at some point over my life, I stopped counting surgeries. I stopped counting at 250 because, to be honest with you, what was the point?

I did marry a wonderful man. We have great children, four grandchildren. And so for that part of my life, I am so grateful.

But, again, I think about what if. What if I hadn't had this disease and I'd been able to read my child a book at night? Something other parents take for granted I couldn't do. What if I didn't have a trach and I could have gone swimming with my child? Something I couldn't do. Or simply ride a water ride at the park. Things that, if I did and something went wrong, I could quite possibly die.

I think about what if I'd never had a pharyngeal tear during a surgery, which almost cost me my life? And my children have the memory of me at home unable to get out of a recliner because of the pain. So I think, for so many of us in the rare disease space, there's a lot of what ifs.

When I talk to others and you say the word ‘surgery’, and you think, “Oh, I know someone who’s had surgery.” But imagine those emotions you had when someone you cared about had surgery, when you had to watch them being wheeled out. You had to watch the patient board in the waiting room waiting for them to pop up is complete, waiting for them to get out of recovery, watching that person at home as they recover from the impact of anesthesia, surgical discomfort, all of it.

The anxiety that creeps up as you're preparing yourself or a loved one for surgery, multiply that times 250, and that's my story.

I've been on a cancer drug now coming up almost seven years to try to control the disease. It's off‑label so I never know if insurance is going to pay, not pay. So there's that stress as well. But it has kept me stable.

A really neat thing happened when I had surgery almost six years ago. This voice came out. But what you don't know is for over 20 years before that, my voice was a barely audible whisper. My son, who's now 30, had never heard me with a voice. So that's the impact of surgery on my life.

I remember the day that I found the foundation and I realized I wasn't alone. There's something so healing in that moment when you hear someone that sounds like you. I like to think that that's what the foundation does for patients to this day.

I was asked to take over the foundation coming up on four years, but there was a reason why I said yes. When this voice came out, I said, “God, as long as I have this voice, use it.” Be careful what you ask God for, because He has put me in something that I was not qualified for, but He somehow, in the way He does, has qualified me for it.

When we were selected as a CZI grantee in the Rare As One Network, I was probably in disbelief for weeks. But I can look back and all the success we're having now, all goes back to that yes , thinking that we were able to get in front of the FDA and change their mind on the end points that matter to patients.

We were able to be part of two biotechs that are now in the BLA submission process for potential therapeutic treatments, so that my goal that surgery will no longer be the treatment for this disease. We are almost there.

Because when I think about the whys what I do, it all goes back to Eden, a little girl with the disease and the promise I made myself and her mom that, as long as I'm leading this, I'm going to do everything in my power to make sure Eden and the other children like her do not have my story in my age. Their story isn't about surgery, the PTSD caused by the surgery, the financial instability as a young married family that this disease caused. I don't want my story to repeat itself.

And part of what we've done as an organization is realize that there was no one coming on a white horse to save us. We were going to have to do it ourselves. So if that's hosting a roundtable where we bring together the world's best in RRP care and research, if it's, for all purposes, basically stalking people on LinkedIn to get them to hear our story, to using whatever methods that are available to us that are legal to get our message out there.

Just this past winter, I was invited to speak at the White House for Rare Disease Day. I'm sitting there in this room of the greats in rare disease. I'm looking around at these people that I've looked up to for years, and to be at the table with them was such an encouragement to me to know that we have hope. The hope that my parents were given 52 years ago is real now, and it's because of the patient voice.

And when you see me, I hope you don't just see my story. I hope you see the story of all of our warriors, each of us that goes into the OR, each of us that, at some point along the way, has asked our parents, “Why did I get this and my siblings didn't?” Or the days we question why surgery was allowed to be the only treatment for so long, why that was okay.

I guess if nothing else comes from this, is to bring the message that your voice has power. Even if you feel very unqualified, this community will come up beside you and they will make sure you know what you're doing.

I think that's what makes the rare community so special is we're not in competition with one another. It truly is how can I help you reach that goal, the sharing of information.

The similarities of the patient stories will always amaze me, but I hope I never lose the sense of wonder and what one voice can do for an entire disease community.

Kit Donahue

TRANSCRIPT

Growing up, my favorite part of the day was in the evening when my mom would tell me stories. They helped me feel connected to a larger community and it sparked my curiosity to learn the stories of those around me and to lend a helping hand when I could. That passion led me to pursue a career in community organizing, where I could help more people connect around common struggles and find solutions.

In 2015, I started a campaign to improve access to mental health care in my community. And as I met with community members, I was heartbroken to hear their despair over ever finding a solution and support for loved ones who struggled with a mental illness.

So I eagerly set appointments with researchers and clinicians who were experts in mental health care. And instead of helping us find solutions, we were told that there was nothing we could do. We just needed to wait and let the experts do their work.

It was insulting. I left those meetings feeling this growing sense of frustration. There was a critical disconnect between the family struggling to care for their loved ones and where the researchers and clinicians were prioritizing their time.

When I get frustrated, my coping mechanism is to bury myself in research looking for solutions. I checked out dozens of books about mental health care and pored through government websites to learn all of the acronyms and jargon. The more I learned, the more I saw a need for a bridge between the experts in science and governance and the communities that they serve.

The few initiatives that I found that were working to address that problem were championed by academics and clinicians who could lend the weight of their expertise to the community. So after careful consideration, I decided that, as ridiculous as it might seem, the best way for me to help was to go back and get my PhD.

So, I started interviewing with research labs at my local university and I was intrigued by a group that was working on a rare inherited childhood epilepsy called Lafora Disease. During the interview, the professor showed me pictures of patients with Lafora Disease and told me how their parents had been instrumental in pushing for the researchers to apply for a collaborative grant to accelerate the therapeutic research. And I was thrilled to find a lab that prioritized patient research collaborations.

So I joined the lab and spent the next five years learning how to study rare diseases. And around the time I was wrapping up my dissertation, I learned about an exciting opportunity. The patient advocacy organization for Lafora Disease, Chelsea's Hope was looking to hire a science director in order to help them bring together researchers and clinicians around a new set of priorities that was emerging from the patient community. I applied, accepted the job offer and jumped into the work with enthusiasm.

I started by organizing our annual science symposium inviting industry representatives, clinicians, researchers and family members to come together and discuss progress towards a cure.

I quickly learned that pharmaceutical companies were reluctant to commit resources for an ultra rare disease. And despite my efforts to show that we had a clear therapeutic target and strong pre clinical data to show efficacy in animal models, the conference ended with no clear path forward to getting patients into clinical trials. It felt like a personal failure and I had no idea how to bridge the gap between families and these industry partners.

And, worse, I had this expanding list of skills that I needed to learn to be able to manage the day to day operations of the organization, updating bylaws, establishing advisory boards, creating a social media presence and building relationships with regulatory agencies.

A month after the symposium, I felt completely overwhelmed and I wondered if I had made a mistake in taking on this role.

Then one night, after a particularly frustrating day of sending emails and receiving zero responses, I found myself dreading the upcoming committee check in meeting. I felt like I had nothing new to report and nothing to offer.

It was past my usual bedtime but one of the few times that everyone could meet, because we're spread out over so many different time zones. I was sitting in my kitchen, clutching my cup of Earl Grey tea like a lifeline. It was a smaller group checking in that night than normal. Most of the members on the committee are caregivers for children with Lafora Disease and it's not unusual for them to have a last minute emergency that comes up.

That night, our family support coordinator, Nikki, hopped on for our call looking tired but determined. I knew that her daughter had recently been in the hospital battling multiple infections, so I asked her for an update.

And as she shared the terror of the past couple of weeks, the round the clock vigils, the desperate parade of medications trying to stabilize her daughter, my exhaustion from the work day begin to fade. This was a whole new definition of hard. And here was Nikki online and ready to do whatever it took to help other families work to find a cure for this devastating disease.

While my tasks felt no less daunting, Nikki's story reset my perspective and solidified my determination to keep working, for her daughter, for the other children with that disease like her and for all of their families.

So, I signed off the meeting with renewed energy and I worked late into the night to map out strategies for building our organization's capacity to attract new industry partnerships. And, excitingly, one of those strategies led to the development of a community funded safety study that's going to be starting in November 2024.

There's still much work to do. Every day feels like a race against the clock to get treatment to these patients, but, now, in moments when I feel overwhelmed, I think back to Nikki's story and it keeps me moving forward.

We haven't yet closed the gap between our families and our industry partners, but we are building a bridge piece by piece, and we're closer than ever before.

Thank you.

Mary Vyas

TRANSCRIPT

It is a spring morning. The house is empty and quiet. My two teenage kids have both left for high school, my husband Jay is at work. It's about a week before for spring break and I'm really focused about this spring break trip we're planning. The kids are getting to that age where family trips may soon be a thing of the past.

I'm in my bedroom and I pick up the phone. I'm standing. I'm looking out the window. I notice the trees and the sun on the leaves. The call is from a good friend of mine. She happens to be a pediatric hepatologist.

My 16‑year‑old son, super easygoing kid, a swimmer, fit, energetic, shining with 16‑year‑old health has been having some odd GI problems. His case has landed on my friend's desk, so I'm happy to pick up the phone.

I hear her tell me, “We think he may have something called primary sclerosing cholangitis, or PSC.”

I'm still standing there looking out the window and I'm feeling like, “Well, okay, maybe this is progress.”

I can, in my mind, see exactly what the light looks like on the young spring leaves. You know those moments? I didn't know at the time, but the fact that I remember that moment so clearly, some part of me knew this was a life‑changing moment.

My friend tells me they need to do more tests to know for sure.

It's now about six weeks later. After pokes and scans and biopsies and lots of high‑dose prednisone, after arguments with the doctors when they tell us they don't want him to be more than two hours from the hospital, “Nope, he can't go on his model UN trip that he worked on so hard to go on. Nope, got to cancel that family spring break trip.” After I disbelievingly delivered a letter to the airline from the doctor saying, “It's probably in your interest to refund their tickets because you don't want to have to deal with this kid who might not survive the flight.”

At this point, the words PSC don't really feel like progress anymore, but they feel just kind of like a really weird dream. I just can't connect this to this kid who gets up at 5:00 AM to go running through the streets of Toronto with his team before they jump in the pool for two hours. It just doesn't make any sense that there's something life‑threatening here, especially something that could be life‑threatening in a matter of hours. It really should feel like a nightmare, but it doesn't. It feels like a mistake.

I'm surrounded by support. I have a wonderful husband Jay, we have wonderful doctors. Every test that they have asked for has been made immediately available, but I feel completely disconnected and alone.

We've learned that PSC is a rare liver disease. We've also learned, well, something we already knew but we didn't really think about too much, the liver is well named. You do need a liver to live.

So we're in an exam room, we're at a hospital, which is called Sick Kids, which didn't feel very good. The room is oddly large. I'm sitting next to my husband. I'm feeling really claustrophobic. I've got coats on my lap. I've got a big binder I've been taking notes, and I've been recording every test. We're getting that talk, the talk now that they know. The diagnosis has been confirmed. He has PSC and we're getting the talk about what this means.

What it means is that there's no treatment. They don't know what causes it. They don't know why my son gets it, or anybody else. It doesn't get better. It is progressive and there's really not a very accurate prognosis about when. It could be today, could be tomorrow, could be 20 years that his liver fails.

I feel like I'm on a roller coaster that's just going down. There's no up, but it's still like this alternate reality. I'm sitting there. I'm looking at this man‑sized teenager across this large room sitting on a child‑sized bed exam table. Something is just not right. Seems like just yesterday, we were worried about how much time he was on the computer and whether or not he had put his swim cap where the dog couldn't eat it.

So the doctor starts telling us that there is the life‑saving possibility of transplant. In fact, Toronto has a very big, one of the largest, transplant centers in North America. And in fact, the transplant center in Toronto happens to be a world leader in the living donor liver transplantation.

Wait a minute. What? Living donor? Liver transplant?

Aside from the hope that this has all been a big mistake, it's the first time in this I feel a whisper of hope. Is the roller coaster maybe starting to head up? This mama bear is all in. I have just heard that I have it in me to fix this. I can fix this with my liver. Done. No questions. No decision. Let's go.

I feel like I'm waking up. This is not a new reality. It's just a little detour. Off he goes into the future we planned, with his shiny health and his shiny new liver.

Gently, Dr. Ling brings me back into the alternate reality. Yes, transplant is possible, but not now. It's risky. You have to survive the transplant and then you exchange the disease for needing to be on immunosuppression the rest of your life.

Okay. Not now, but when?

Nobody knows.

I'm feeling whiplashed by the up and down.

So, time goes on. I still cling to this hope that I've got the fix in me. And, of course, I throw myself into learning all about it. I want to be ready to jump.

It's pretty amazing. Did you know that you can take a piece of your liver and it'll grow back in three months, be fully functional. It's kind of like an internal haircut.

I also learned that I have until 60, at least in Toronto. After that, I or my liver will be too old to be a donor.

So, I go on and I'm in this frustrating limbo. Of course, I don't want my son to need a liver transplant, but I also don't want to lose the chance I have to fix this for him.

I throw myself into work. I start a Canadian affiliate of the US‑based PSC partner seeking a cure. I get busy. I learn all about PSC, and the years go by. And as the years go by, the expiration date on my liver as a fix for my beloved firstborn gets closer and closer.

So, while I'm learning all about living donor liver transplantation, I'm also learning all about PSC and liver disease. I learn that living with a sick liver is really hard and that people with PSC die all too often. And that people with other liver disease die all too often, especially in North America. We don't have enough organs for transplant.

At some point in these years, I come to the realization that I will be a donor, regardless of who the recipient is. I don't really remember making a decision, but I know that if I cannot fix this for my son, well, I have to offer it to somebody. I really can't explain why that was such an easy decision to make. Maybe too many people I now love in the PSC world need livers. Maybe it's the amount of loss and pain I'm witness to, being part of the rare disease community. What I do know is that spring break trips and swimming fast now are completely irrelevant.

A few months before my 60th birthday, I submit a form. I check a box on the form that says I would like to be a non‑directed donor, and the transplant center will get to decide who will be the recipient.

A little over 7 months ago, in honor of my 60th birthday and the expiration date on my liver, I wake up early. I get myself to the hospital. I check into the surgical unit. I get the IV. I get on the gurney. I'm waiting in the curtained area with my husband Jay.

A man shows up and says, “We got to go now,” and I go on a gurney sprint, just like a TV show, doors banging, bright lights. Next thing I know, I'm in the OR. It's calm. It's orderly. And I just remember being so thrilled and relieved.

Next thing I know, I'm waking up. I am overjoyed. I am amazed and I am in no pain.

My husband takes a video and I'm just so happy in that video and, again, amazed. I may be a little loopy in the video. I think I say the word ‘amazed’ 10 times, and I also say, “Everybody should do this.”

I don't know who received two‑thirds of my liver. It is, of course, beyond bittersweet that it was not my son. I'm beyond sad that I haven't been able to fix this PSC for him yet, but I'm leaning into gratitude that his original liver is still hanging in there.

I physically am totally fine. I have a beautiful scar. You too can have one. I had a few months of recovery while my liver regrew, taking a break from my PSC work. Mostly, it was just a lot of sleep and staring out the window. Different trees, different year, but the same spring light on the leaves as that day 10 years ago when I first heard the words primary sclerosing cholangitis.

Lakeia Nard

TRANSCRIPT

So, here I am pregnant with my fifth child after four miscarriages. He was kicking strong. I was excited. And the day he was born, it was a wonderful moment. I knew he was going to be something special then.

We get home. He spent a week with jaundice. So while I'm on bedrest, he's back and forth in the hospital dealing with jaundice. Then it took him like forever to open his eyes, at least two weeks to get his eyes to open.

He seemed like a normal kid. He started to develop normally. He had some neck range that I was concerned about and so I talked to my pediatrician and he referred me to therapy.

Again, he was still thriving and I was just assuming like, okay, it's just joint stiff neck. He was born I'm an older woman at the time that I had him. And as he continued to grow, I'm starting now to notice delays, so we continue to take him to therapy.

He finally walked at about 15 months, but he walked with a gait. So I was like, “Okay, well maybe he's learning to walk.” It's kind of different and so I expressed that to, again, his pediatrician.

At first, he kind of just blew it off. He just sent me to get him diagnosed because he was diagnosed with developmental delay and then autism. And he kind of made an assumption, like maybe it was because he was autistic.

I was like, “I don't think autistic kids fall but okay.”

We continue with the therapy and, not even a year after walking, he starts to fall quite often. And he would get up using his knees as if he was an old man.

So I go back to the pediatrician and I say, “Okay, something is extremely wrong. He is falling often and when he gets up, he gets up like it's painful, like he's an older man.”

So we were referred to a neurologist in Louisville, which is two hours from where we live, and at a muscular dystrophy clinic. As she continued to work with him, she assumed right off the bat, “Well, it's got to be muscular dystrophy. It's got to be.”

So we did the whole go over what muscular dystrophy is. I get home, I do some more digging. I go to the support groups, ask more questions and it just didn't line up.

So, I call her back. I'm like, “We need to make an appointment, because I don't think this is right. This is not muscular dystrophy. This is not sounding right.”

So she lets us come back in for another appointment. She does more testing and she's like, “Well, he does have some ____ [?fasciculation? 03:46] movements in his tongue and I'm seeing this all the time in my SMA patients, you know, the way that he's moving and he's falling and he's losing mobility. If it's a duck, it's a duck. If it quacks like a duck, it's a duck.”

And I'm like, “Okay.”

Again, I go home and now I'm in the SMA support group. I'm researching that and I come back to her. I'm like, “I don't think this is it either.” I was like, “It's not aligning with my son and how he acts and how he maneuvers.”

So she continued to do the research. She sent his case overseas. I'm just devastated. Like, how do I tell my other kids who just adore him, because he's the baby? He's extremely spoiled. Like, how do I tell them that he's going through this? Like, he could possibly be in a wheelchair.”

It was happening so fast. To watch my son learn all of these milestones that every mother is just so excited for their baby to learn, watching my son lose all of those same mobilities.

So we get back. It's not SMA, it's not muscular dystrophy. We're doing the muscle biopsies. At one point, we had to do a sweat test to make sure he didn't have cystic fibrosis, because he always got sick and he always got a fever and I never knew why.

So, we're doing all of these testings. She sends his case overseas and there is nothing. So she's telling me, “Well, we can't do any testing until he gets hospitalized again.”

And so I'm stuck just like I want to know but I don't want to wish that my son is hospitalized again. But as he continued to grow, he had a pattern of being hospitalized around the same time so I knew he was going to be hospitalized eventually.

And when he was, we did a whole genome sequencing and the NIH reached out to say that they had a hit on a gene mutation which was SPTLC2, and only one other person has ever been seen with that.

So we flew to the NIH. They do their testing and they say he has a form of pediatric ALS and enjoy him and you need to be thinking about if you would want him on machines or not.

We fly home with nothing. No resources, no new hospital to go to, nothing. I was just stuck. I couldn't believe it. Like he's going to die? We went from all of these other diseases where he could potentially live a full life to he's just going to die and enjoy him.

So, I did that. I enjoyed him. I let him be the kid that he wanted to be. Even if it was me going down the slide holding him, I made sure of him. So he went from walking to running me over with his wheelchair and thinking it was funny. I knew in the back of my mind, but I didn't want him to feel that energy from me, so it was going to be okay.

Reaching out to family and friends, the alienation was severe. It was like everybody just kind of just disappeared. Here I am having to pick this child up and move him all around the house because he is autistic, so he has needs that he wants to do. And if you're familiar with any child with autism, they're very demanding. So I am actively moving nonstop because I am his legs, I am his arms. And I'm watching him slowly regress to where he can't pick up to feed himself anymore, to where he can barely move around in his power chair.

We got through COVID and I was excited. I was like, “Yeah, we're going to make it!” In my mind, I was like, “Okay. Maybe when he gets around ten, I'll be more focused to say what's to come. I can think about it then. But right now, he's great. He's doing fine. He could live like this.”

We got through COVID. He didn't get sick and I was like, “Yeah, we're going to be okay.” And we wasn't. He eventually ended up getting sick again with rhinovirus and it completely shut his lungs down. We spent four months in the hospital. They tried three times with incubation. It didn't work so we had to do the trach and we went through that whole surgery.

Eventually, I was able to bring him home on a Do Not Resuscitate and on palliative care. He was doing better. He was picking up weight. He was getting in the motion of being back at home, which I kind of brought his whole room to the hospital. Because I was like, “As long as he's going to be here, he's going to be stiff. He's going to lose what mobility we have.” So I'm bringing video games, I even brought his wheelchair. Like, since we're here, this is going to be your bedroom.

So when we got home, he was he was ready to continue his day to day thing that he does at home. I eventually, by way of force, through court, he had to go see his father. We all did the training. And he passed away with his dad the day before he was supposed to come home to me. I would go over there every day, all day. I still went over there to do his medication. And every time before I leave, I'm like, “You ready to go home,” because I secretly wanted him to come home, so bad. And every time I'm leaving, I'm like, “You want to come home?” And he didn't. He was fine. He enjoyed his dad. They had a great connection.

The day before I was supposed to pick him up, he passed away. He called 911 and they resuscitated him, even though he had a DNR. He became brain damaged. I remember leaving the nail shop doing 90 to his house. And when I got to his house, the ambulance was pulling out and I was on the ambulance’s tail.

When they got him in the room, he looked at me and he smiled and went into full-blown seizures. And my baby was brain dead.

So, I bring him back home, because I wanted him to pass around family and not in the hospital. He made it past his 7th birthday on the machines. Eventually, it was time to take him off, because now he was having seizures again. So, I was told that it was time to take him off the machines.

It's crazy, because when I took him off, he lived a day and a half without the machines. And he passed away on Rare Disease Day at 7:14 PM, which both are my favorite numbers.

The nurse called and I had him sent for his autopsy to donate his samples to the NIH so that I could focus on finding a cure or a treatment for it. I felt like I couldn't save my son, so I'm going to save someone's son.

That's when Melanin Children Matter was born. I do this for King Nazir, my forever baby who is now my forever angel. That is how I will continue to keep his legacy alive.

Emily Ventura

TRANSCRIPT

When my first and only daughter was five months old, we were visiting family in Wisconsin. I'm originally from Kentucky. When we were there, she was very tired and lethargic, which was unlike her because she spent her entire first months of life crying, so we were very used to an active and vocal child.

We were told that she had colic. I also didn't know what colic really meant because colic is just a crying baby, but her pediatricians assured us that this was just babies. They cry. We'll give her gas drops, indigestion, all those things.

So when we were visiting my parents in Wisconsin, I noticed that she had some weird bruising on her back. The bruising looked like fingers. It looked like when I had held her, my fingers had left bruising.

I noticed it and I called her doctors at home and they said, “Okay, just bring her in for lab checkup when you get back. Keep an eye on her and it shouldn't be anything, but we'll check some bloodwork when she gets back.”

Two days later, we were waking up to take the flight home. When my daughter woke up, her shoulder was swollen, very obviously swollen. That's when we felt concerned. Rather than going to the airport, we went to the emergency room in my parents’ hometown.

Kind of just figured, well, that's weird. She had had an ear infection. She was treated on antibiotics. I just figured there was something that she needed to regulate.

Went to the ER and was not really prepared for what happened next. At first, they saw the bruising and they worked us up for an abuse case. Once they got her bloodwork back and realized she was in liver failure, they apologized and admitted us to the pediatric ICU.

When we were in the ICU, I was with my daughter who was no longer crying all the time because she was sleeping all the time, because she was in liver failure. I thought I was going to lose her in that moment. The doctors didn't know what the reason was. They did a lot of tests. There was a lot of questions. “Did you give her Tylenol recently? Did you give her too much Tylenol?” I don't remember. That was at home. Maybe I did give her too much Tylenol. I started questioning every little thing that I did.

They just kept on going with their workup and didn't really have any answers, but she did end up stabilizing after two days, and stabilizing as in she's no longer in liver failure but they still didn't have an answer.

So we moved out of the ICU and, a few days later, she was stable enough to go home knowing that she had some sort of liver condition or liver reaction to something, but she was not in any immediate danger of her life, so they sent us home to Kentucky.

I was an ICU nurse at the time so liver failure was one of the specialty populations that I took care of. I knew enough to be scared that I had an infant at home who had recently been in liver failure. I knew what stability looked like in the short term, but I also knew how quickly things could progress to unstable. And so I started worrying about every little thing.

We were supposed to follow up at our local specialty hospital, which was two hours from us within four weeks of getting home. When we got home, she was crying, she was uncomfortable. I just felt like something was wrong and so I took her back to the ER.

The ER took my concern seriously. They shipped us off to that specialty hospital that's two hours from us. We spent a week there and still didn't have an answer, but they performed liver biopsies. We knew something was wrong. The specialty team confirmed. It could be this whole slew of things. They didn't all sound great, but we were just going through the motions.

I really liked the doctor who was with us in the hospital. She was somebody that instilled trust in me right away. Being an ICU nurse, that's not easy to do. I don't try to but I question everything, which seems like I'm questioning everybody. It's more just educated questions and so I recognized that I could be a challenging mother to a patient, but she and I got along really well.

So when we were getting close to being discharged, I was looking forward to following up with her just because I felt comfortable with her. She informed me, “This is my last day at this hospital. I'm going to a hospital cross country and you’d have this doctor,” who came in and introduced himself. He felt less warm. I didn't know him. We were going home and we were supposed to follow up with him. And then I just felt very concerned.

We ended up going home. A few weeks later, back for outpatient with this new doctor. On our way to the appointment, I called a good friend of mine and I told her the name of the disease that the hospital had given me from the genetic test.

I said, “I don't have time to look it up but we're just a few minutes from the doctor. I just wanted you to kind of take a look and, after the doctor, we'll reconnect.”

Went into that appointment. The doctors came in, said, “She has progressive familial intrahepatic cholestasis,” which I already knew. And they said, “What questions do you have?”

I just paused and said, “Well, I know nothing, so I don't even know what questions to ask.”

It was then that I found out that there really wasn't many answers. This was not a positive diagnosis. This wasn't like a, “Here's your diagnosis and here's the treatment path and she will do better once on this course.” This was, “Her disease will progress towards liver failure requiring liver transplant at an unknown point in time. She will likely experience severe itching, itching that will keep her up at night. Really, there's nothing to manage the itching. She won't be able to absorb vitamins or fats, and gaining weight would be really hard so you'll have to keep coming back to us every few months while we monitor her to make sure she's doing okay.”

They didn't have any resources to give me. They didn't have any support. I was very confused.

Left the hospital, called my friend and my friend was crying. She had looked it up and the information that was available on the internet was very scarce but it was not very good.

That was the start of our journey.

A few months later, we were dealing with the itching pretty severely. Every night, we would wake up to her sheets in her crib being bloody. She would scratch her ears nonstop until they bled. We had to keep her covered head to toe with a onesie because if she had any skin exposed, she would scratch it until it bled.

During the days, she couldn't really play or eat or do much because she was just scratching, so it was a nightmare.

They added one medication. It's an off label medication. It's something that works for some patients, not all. That didn't work. So then, we were faced with surgery as an option. But the surgery is for symptom relief. This was not transplant. This was for the itching.

There were two available surgeries that helped some and not all. One was an internal diversion, one was an external diversion, trying to divert bile away from the liver. The external diversion comes with a stoma, so a bile bag that's external to her body. The thing is, they couldn't tell me which one was preferred. They couldn't tell me which one had a better shot of her doing well. They couldn't even tell me if the surgery would help her itching, but it was our only hope.

We tried the external diversion. It didn't work. So now she was 15 months old and she had an external drainage bag that was just another area to scratch. She would scratch until the bag came off and she would scratch her stoma until it bled.

We did everything we could to try to figure out how to give our toddler a sense of a normal life while she was dealing with this itching, all the while going to the hospital a few hours from us every three months so that we could ultrasound her liver, get bloodwork, and ultimately see if her liver was progressing towards failure.

That was her first five years of life. When she turned five, her bloodwork changed. Her itching was no longer her primary problem. Her liver was starting to fail. Her spleen was enlarged. We knew this was coming. Her vitamins were so low that any type of vitamin therapy wouldn't help her, and there's grave consequences to chronically low vitamin levels, so it was time. It was time to talk about transplant.

Fortunately, we were able to be a little bit proactive. Remember that doctor that I mentioned early on, the one that I didn't trust because I didn't know him? It took us about a year, but we really got to know each other well. I learned that he actually was one of the most prominent researchers in the field.

He had treated two patients with PFIC at that time. At first, I said, “Well, two patients? There's no way this guy knows anything. Obviously, I need another opinion.” But, actually, he knew more than most. Two patients was quite a lot.

So with his support, we proactively listed her for transplant. She was low on the list because she wasn't in severe liver failure just yet. Two of our friends stepped up to be a living donor, which is a really great thing, but fast forward, it made me really uncomfortable. I wasn't able to be a living donor, neither was her father, because we were unsure as to how the genetics played in, if that was favorable to transplant a liver that would have a component of this disease, so these two friends were our options.

But I had a lot of concerns. They pressed on, did the evaluation. One of them was pretty much primed and ready to go. She had one more test to go. She was going to donate a liver to my daughter. It's actually the same friend that had that call the day of diagnosis.

I was working a shift in the ICU and I just felt sick. I had a panic attack. All of a sudden, something just consumed me. “She can't do this for her. She just had her firstborn child. She's still breastfeeding. She worked really hard to have her child. She can't put her life at risk for my daughter.”

The next morning, Cedar, my daughter received the call that there was a donor available, a cadaver donor available for her, so she was ready for her liver transplant. I don't know what it was. I don't necessarily believe in fate, but that day, that panic, I was so worried about my friend and the next day the miracle came, or so I thought.

My daughter is doing so much better after transplant than she was before, but her disease is by no means cured. She was transplanted at age five, she's now 13. Since then, she's had five episodes of rejection, she's had reoccurrence of her disease, of her underlying disease and all of the itching and everything that went with it, and just last month, she had a seizure while we were driving home from labs.

She was helicoptered over to the hospital where, fortunately, she is okay, but now she has that on her plate.

So, on the day to day, she is a 13 year old living a beautiful life, showing all of the amazing qualities that she has, all of her resilience, her fearlessness, her ability to cope and adapt with life. She just wants to live as a normal teenager and I want to provide that for her. But on some level, I'm still waiting for that next bomb to drop.

Axel Lankenau

TRANSCRIPT

First of all, I'd like to say it's a real privilege for me to be given the opportunity to speak to so many wonderful people. At that time of the day, I'm very grateful that you listen another 10 minutes to my story. Thank you.

It was the summer of 2005. I was sitting in the doctor's office and waiting for the results of an MRI scan for my first son, Jonas. he was six months old when seen because of developmental delay. They diagnosed a pontocerebellar hypoplasia type 2. I had no idea what that meant. Cerebellum? What for? The neurologist told me it's about coordination and motorics.

I asked her, “Does it mean Jonas will never learn to play the piano,” because he cannot move his hands independently. This, for me, would not have been such a big problem. I can't play the piano either. “Or does it mean he will never learn to ride his bicycle,” because maybe he couldn't balance on the bike. This, at that time, was the most severe impediment I could imagine for my son.

She answered, “It will be somewhere in between.” Then she gave me a small handwritten note, “PCH2, Professor Bart, 1995”.

At home, I Googled it. PCH2 is an ultra rare neurological condition due to severe underdevelopment of the brain. There were 16 kids in the study, none of them ever learned to sit, walk, talk or grasp. Typical symptoms were severe epilepsy, apnea, sleeping disorder, lots of respiratory issues, feeding and digestive problems, and ten out of these 16 kids died before they entered school. No treatment available.

This could not be true. No way.

Three months later, the engineer in me confronted my son's new neurologists with the before and after analysis of Jonas's progress. July, no head control at all. October, great head control. At least I thought so. July, no fixation at all. In October, his eyes followed toys as if they were magnetic, and so on.

However, the doctor made clear, “Great approach, but, unfortunately, the MRI and, thus, the diagnosis are crystal clear. Your son will never live an independent life.”

Devastating news and definitely far away from this piano bicycle thing.

He continued, “But from over 30 years of professional experience, I can assure you that every child has a frame of development. You can think of it as a picture frame. The size of the frame is different for each child. It depends on when the child was born, where they were born. Sadly, also on the financial status of the parents and it very much depends on the genetic disposition.”

“Jonas's frame,” he continued, “will be much smaller than the one of a child without PCH, but it is there. And its size is definitely not zero. The best you can now do for your son is to help him to live a good life within his frame.”

That's exactly what I've been doing since that day.

Months went by and the more Jonas stayed behind in the development, the more I realized that we were supposed to live our life in the parallel universe of the disabled people, similar to muggles and wizards in Harry Potter. At that time, standing in Jonas's room looking out of the window into the garden and realizing that I never will be able to play soccer with him made me cry.

In February 2007, Jonas's brother Felix was born, all pre and post natal tests showed a healthy boy who behaved wonderfully normal and completely different from Jonas in his neonatal period. Felix opened a completely new perspective, a foothold in the other universe. There was relief, hope and some kind of normalcy. Felix got a soccer ball for Easter.

But life had other plans. On a July evening at 6:30 PM, the lead neurologist and the director of the children's hospital herself walked down the aisle to Felix’s room. In this very moment, I knew what they were going to say, the same MRI as Jonas. Felix also had PCH2. No soccer in the garden. Nothing. Never.

The same evening, we drove back home from the hospital along a winding road through the woods. This was the only time ever I thought for a brief moment whether it would be better to run the car into one of the next trees. Obviously, I did not.

However, two severely disabled sons with the need of 24/7 intensive care, no treatment available, no support system, no idea what’s to come, this was what summer 2007 felt like.

Coping with this situation was not easy. It took me a while to accept that life was going to be completely different than what I dreamed of. Slowly, I realized that even though PCH2 was ultra rare, we were not alone. Together with other PCH parents, we established a virtual exchange platform and organized our first in person family meeting in 2008. We learned to support each other. We parents became the experts for our children.

We kicked off a series of biannual meetings for the families. We invited scientists and doctors to these meetings. We parents initiated the first ever natural history study on PCH2. Over the years, I became fine with looking out of Jonas's window and watching my sons in our garden enjoying to swing in the hammock, in the sun, which was in their frame. No more tears about not being able to play soccer with them, which was out of the frame. Life turned out to be different, but not necessarily worse.

In 2018, seven PCH parents founded PCH Familie e.V., the first registered patient organization for families living with PCH2. Our exchange platform grew to the most comprehensive source of information on PCH2 on the planet. We started fundraising to support science and to organize future family meetings.

The biggest of these meetings just took place in July this year, our Cruise4Life, 28 children living with PCH on board of a cruise ship on the Baltic Sea among 6,000 other passengers.

In 2019, we kicked off PCH2cure, our patient driven research initiative of basic researchers, clinicians and us parents, a small group of very committed people sharing an ambitious vision to find a cure for PCH2.

On December the 1st, 2022, my son Felix plunged into the biggest crisis of his life so far. Severe central fever hit him and almost killed him seven weeks later. And on the very same day, CZI publicly announced that PCH2cure received the brilliant $2 million PPC Grant, a complete game changer, the most important news for PCH2 families since the gene was found back in 2008.

Eventually, there was some hope to at least widen the picture frame for PCH2 children. This hope led me to my first CZI Science and Society meeting last year in September. There, I was completely overwhelmed by the power and the confidence in the room.

In the morning of the first day, we just heard it, Michael Hund from EB Research held a brilliant keynote and told us, “Be a buffalo and run into the storm.”

In the evening, Brian Wallach from I AM ALS told us via Zoom, “My generation is the first one that will not die from ALS.” What a powerful statement.

Exactly 18 years after having been told the story of Jonas's picture frame, this day in Newport Beach last year changed my life mission from improving the quality of life of my sons within the picture frame to get rid of the whole frame for all of the children with PCH2.

Before going to bed that day, I texted home, as of today, I'm 100% sure that Jonas and Felix will still be alive when we find a therapy for PCH2.

Thank you.