Case #33: Phoebe

Summary

Symptomatic: A Medical Mystery Podcast

Case #33: Phoebe
Host: Lauren Bright Pacheco (iHeartPodcasts)
Release Date: December 23, 2025

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Overview

This episode follows the harrowing, decade-long diagnostic journey of Phoebe Marshall, a now-teenager afflicted by mysterious, progressively debilitating medical symptoms since infancy. Through candid interviews with Phoebe, her dedicated mother Sarah, and their medical team, host Lauren Bright Pacheco unpacks the immense challenges posed by rare, undiagnosed diseases—including repeated medical dismissal, emotional turmoil, and the immense burden on families—ultimately highlighting the life-changing power of determined patient advocacy and the transformational work of the Undiagnosed Diseases Network (UDN).

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Key Discussion Points and Insights

1. Early Onset and Escalating Symptoms

• Infancy to Kindergarten:
  • Phoebe was sick more frequently than her three sisters, starting with severe pneumonia at 6 months ([03:11]).
  • At 2.5 years, she developed a historic sinus infection, requiring unusually powerful antibiotics for her age ([03:43]).
  • Prolonged antibiotic use led to severe GI issues—her mother, Sarah, sensed the doctors doubted her reports, suspecting Munchausen by proxy ([04:59]).
• No Clear Diagnosis:
  • Multiple specialists ran immune system testing; results pointed to a “dysregulated” but not diagnosable immune issue ([06:20]).

2. Early Childhood: Chronic Pain and Rare Symptoms

• Chronic Pain Begins:
  • First memory of pain: persistent ankle pain disrupting sleep, resistant to explanation or treatment ([07:23]).
• Vision Issues:
  • By kindergarten, Phoebe had to wear an eye patch due to black spots in her vision and was diagnosed with retinal vasculitis—again, doctors had no clear cause ([08:28]).
  • These uncommon, disconnected symptoms began to highlight the complexity of her case: “I became apparent very young that I was not a cookie cutter case.” – Phoebe ([08:59]).

3. Acute Episodes and Hospitalizations

• Severe Abdominal Pain:
  • At age six, Phoebe experienced excruciating abdominal pain, leading to an ER visit with sky-high liver enzymes, but still no diagnosis ([10:41]–[12:35]).
• Surgeries Begin:
  • Age 7: Persistent, unexplained stomach pain led to exploratory surgery. Surgeons found and removed mysterious, extensive abdominal adhesions (scar tissue). Pain immediately receded ([13:50]-[14:45]).
  • Six months later, adhesions reappeared. Surgeries became routine every 7–8 months ([15:24]).

4. Prolonged Uncertainty and Emotional Impact

• Living with a Mystery:
  • Phoebe underwent countless procedures, missed school due to repeated surgeries, and endured ongoing doubt from health professionals ([17:14]–[17:47]).
• Emotional Toll:
  • Therapy became critical for Phoebe and her family, grappling with mistrust, dismissal, and the complexity of chronic illness ([18:44]-[20:25]).
  • “I've been taught over and over that no one wants to hear it… it’s really hard to explain to my friends.” – Phoebe ([20:35]).
• Systemic Doubt:
  • Mother and daughter both felt skepticism from doctors; even “helpers” like their psychologist initially doubted the legitimacy of Phoebe’s case ([21:53], [22:17]).

5. The Breakthrough: Undiagnosed Diseases Network

• Relentless Advocacy:

  • Sarah’s tireless internet research led her to the UDN, which investigates rare, undiagnosed cases ([24:24]).
  • Application to the UDN brought validation (“…the first time in talking to a complete stranger that was curious and interested and validated that we weren't crazy…” – Sarah, [24:57]).

• Massive Testing and Red Herrings:

  • Clinical evaluations and genetic sequencing (exome, then genome) in Boston found no immediate answers ([26:21]-[27:48]).
  • Meanwhile, Phoebe underwent spinal fusion for anatomical abnormalities; post-op infection required five additional surgeries ([26:52]-[27:19]).

• Definitive Diagnosis:

  • Genome sequencing finally revealed a loss-of-function mutation in the GDF11 gene—a condition so rare it had no established treatments ([28:25]).
  • “For people that live undiagnosed, it’s a dream come true. It’s like, oh, this is the name; this is the diagnosis.” – Sarah ([28:41])
  • Phoebe: “Honestly, I don’t think I understood the gravity of it… I wouldn’t be where I am without the UDN and the GDF11 diagnosis.” ([29:15])

6. The Science of GDF11

• Explained by Dr. Hugo Bellin:
  • GDF11 is a broad-acting hormone-like protein, influencing bone, muscle, brain, and connective tissues ([31:36]).
  • Research using fruit flies helped establish the gene’s connection to Phoebe’s symptoms, including bone and gut morphological issues ([32:05]-[32:53]).
  • Dr. Bellin commended Sarah’s activism: “She’s been really an advocate for the Undiagnosed Diseases Network because of her experience trying to… help her daughter.” ([33:18])

7. A Tailor-Made Treatment

• Innovative Drug Repurposing:
  • Inspired by precision medicine, Sarah sought out Dr. Matt Meite, who hypothesized Phoebe’s mutation created excessive inflammation ([33:47]-[34:57]).
  • Humira (adalimumab), a common anti-inflammatory used for autoimmune diseases, was prescribed off-label.
  • Result: Phoebe has not needed adhesion surgery in over four years ([35:39]).
    • “She has not had one surgery for her adhesions. So in four years. Over four years.” – Sarah ([35:39])

8. Advocacy Turns Outward

• Sarah’s New Mission:
  • Sarah now works with the UDN’s Patient Engagement Resource and helped establish the Undiagnosed Diseases Network Foundation (UDNF) ([36:59]).
    • “A foundation…created by patients for patients to support patients and families and also support the quest of finding answers for all undiagnosed patients.” ([36:59])
• The Power of Resilience:
  • Phoebe wants to give back as a future social worker: “Truly becoming the person I needed when I was a kid… being a social worker is kind of my way of giving back to people who believed in me when I couldn’t believe in myself.” ([38:35])

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Notable Quotes & Memorable Moments

• Phoebe on Being Dismissed:

  “I promise you, like, on everything I love, this is real.”
  — Phoebe Marshall ([00:45], repeated theme)

• On Parental Advocacy:

  “My mom is probably the most impressive woman I’ve ever met… I am so lucky to have a mom literally rise at dawn for me. She will do anything for me.”
  — Phoebe Marshall ([36:21])

• Doctor’s Recognition of Parental Activism:

  “She’s kind of discovered that there is a drug that helps Phoebe, and…through connections, she’s the one who discovered these true connections.”
  — Dr. Hugo Bellin ([35:11])

• A Universal Message:

  “If you get up every day as hard as it is and continue the fight, surround yourself with people who love you and that you love, there is hope for a better life.”
  — Phoebe Marshall ([39:47])

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Important Segment Timestamps

• [00:03] – First signs of severe illness as an infant
• [04:59] – Hospitalization and suspicion of Munchausen by proxy
• [07:23] – First memories of chronic pain
• [08:28] – Onset of vision problems
• [10:41] – Life-threatening abdominal episode
• [13:50] – Discovery and removal of abdominal adhesions
• [17:14] – Recurring surgeries become routine
• [20:35] – Emotional impact of chronic illness and medical dismissal
• [24:24] – Discovery of the Undiagnosed Diseases Network
• [28:25] – Genome reveals GDF11 mutation; diagnosis at last
• [31:36] – Dr. Bellin explains GDF11’s role and fruit fly research
• [34:57] – Off-label use of Humira; significant symptom improvement
• [36:59] – Sarah’s advocacy and founding of UDNF
• [38:35] – Phoebe’s hope for the future and desire to help others

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Tone and Closing Reflections

The episode is a powerful testament to resilience, resourcefulness, and the indispensable value of advocacy—both familial and institutional—in the rare disease community. It is candid, heartfelt, at times painful, and ultimately hopeful. Listeners are left with a sense of awe for the Marshall family’s perseverance, the promise of genetic medicine, and the real-world impact of connecting patients, families, and scientists in the pursuit of answers.

Message to Listeners:
30 million Americans live with a rare disease, with an average seven-year journey to diagnosis. Resources like the UDN can be transformative—not just for individual families, but for healthcare as a whole ([38:50]).

Phoebe’s closing encouragement:

“My thoughts are powerful… In the chronic illness world and in just like regular life, you determine the outcome… there is hope for a better life.” ([39:47])

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More information:

• Undiagnosed Diseases Network Foundation: undf.org

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Transcript

[Sarah Marshall]

Ruby, she was not in her seatbelt, literally, like contorting. And she just clearly could not get comfortable. The pain was so severe. And I remember her thanking me for taking care of her as if she thought she was gonna die.

[Phoebe Marshall]

You know, at that age specifically, you see doctors as like literally your heroes. They're supposed to know everything. And so when people were like, oh, I don't know, that was like, oh, what do you mean you don't know?

[Dr. Jade Rafferty]

I am ashamed that I did contribute to some of that skepticism when I first met them. I didn't fully understand at that point in my career how complex a brain and body can be.

[Phoebe Marshall]

I promise you, like, on everything I love, this is real.

[Lauren Bright Pacheco]

How terrifying would it be to fight an unknown enemy, one you didn't recognize and didn't see coming? What if that enemy was coming from within? A disease that even doctors couldn't identify? Nearly half of Americans suffer from some chronic illness and many struggle for an accurate diagnosis. These are their stories. I'm Lauren Bright Pacheco and this is Symptomatic. Sarah Marshall is without a doubt on the list for mother of the year. Having come from a background in social work, she has taught her children the value of community and the importance of advocacy. She is smart, intuitive and fierce in her defense of what's right. She is a mother to four daughters that span eight years.

[Sarah Marshall]

My girls are incredibly close. Growing up, they didn't fight all that much, but when they did, I would basically tell them, that person is your sister and she will be your sister the rest of your life. And you can't treat her like that. I only remember saying that maybe once or twice, but they still talk about that message. It's really a special bond that they all have.

[Lauren Bright Pacheco]

The youngest of Sarah's daughters is Phoebe.

[Phoebe Marshall]

My name is Phoebe Marshall and I'm 17 years old.

[Lauren Bright Pacheco]

How do you spend your time when you're not in school?

[Phoebe Marshall]

I work at an after school childcare program that takes up a lot of my time. I really like working. I'm a pretty average teenage girl. I hang out with my friends, go on food, trips, homework, all the regular things.

[Lauren Bright Pacheco]

And I'm sure that being the baby of the bunch, Phoebe grew up with four mothers in the house.

[Sarah Marshall]

Indeed, very much influenced by the inspirational.

[Lauren Bright Pacheco]

Work that her mother does, Phoebe has already made the decision to follow in her footsteps professionally.

[Phoebe Marshall]

I am going to study social work. I want to first be in the child welfare system with cps and then once I get married and have kids and need a more slow moving job, I'M going to be a school social worker.

[Lauren Bright Pacheco]

From an early age, Sarah noticed that Phoebe seemed to be getting sick more frequently than the other girls had. This wasn't your first time in the rodeo. You had three children already. Was there a moment that you remember thinking, something here is different?

[Sarah Marshall]

I remember the first time that Phoebe got sick. She was six months old and she had pneumonia. I have photos because it was Christmas and I remember my family members saying, she looks really sick. Sarah, as it turned out, it was kind of the first in a series of her getting sick or having there be an issue getting better and thinking, okay, that was just a fluke. That's not going to happen again.

[Lauren Bright Pacheco]

As Phoebe grew, signs that something was wrong continued to pop up.

[Sarah Marshall]

The next time she was really sick, she. I was about two and a half and she just was not getting better. I'd brought her in several times. They gave her antibiotic and maybe she was a little better, but not great. And then they did a steroid run and that still didn't get things better. And so I ended up bringing her into the ER because she was having trouble breathing one night and they admitted her, which I was, I remember being surprised about. They wanted to do a CT of her sinuses and I just thought, that's ridiculous. She didn't really have a runny nose. It seemed more like a cough that was bothering her. And as it turned out, the doctor, the ENT that read the report from the radiologist, he said this is the worst sinus infection he's ever seen in a two year old. She was put on an antibiotic that I later learned two year olds are not put on. But she was on it for eight weeks.

[Lauren Bright Pacheco]

Sarah brought Phoebe home hoping this antibiotic would fix things. But after eight weeks on potent antibiotics, new symptoms manifest. Phoebe begins to show signs of gastrointestinal issues so severe that Sarah rushes her back to the hospital.

[Sarah Marshall]

They ended up admitting her. And what I realized in that hospitalization is that they didn't actually believe me. They were basically testing to see if I was lying, if I was making it up, if I was exaggerating.

[Lauren Bright Pacheco]

What did they think that it was? Munchausen by proxy. Munchausen by proxy is a mental health condition in which a caregiver fabricates or induces illness in their dependent to gain attention or sympathy. The condition can also be known as factitious disorder imposed on another OR or fdia.

[Sarah Marshall]

They never said that. I assume that's what they thought because this doctor, I remember him coming in and him just being he was just very doubtful of what I was saying. And then they confirmed like, oh yeah, she does have some of the gastritis from the antibiotic. And so they discontinued it. And I said, well, what are we going to do? What's the other option? And they didn't actually put her on anything more. And I said, but we were just here at the same hospital and they said, this is the worst infection they've ever seen. And we're just, she's going off of it. They basically said yes. They did not send her home with any antibiotic.

[Lauren Bright Pacheco]

So how were the doctors explaining these early health struggles?

[Sarah Marshall]

They really weren't. We went and saw one of the doctors in this practice that I had seen, you know, years prior. And she was an immunologist and she did some pretty extensive immune system testing. And she basically came to the conclusion that Phoebe's immune system was dysregulated. It was kind of hyper reactive, and she had some low immunoglobulins, but nothing that fit a diagnosis that she could have regular treatment for. And so they put her on kind of a prophylactic antibiotic that kept her from getting infections. She didn't really have a real specific diagnosis other than frequent infections. And she really, for the most part, infection wise, was pretty good.

[Lauren Bright Pacheco]

By around four years old, Phoebe began to recognize herself that something was definitely not quite right. When is the first time that you remember your earliest memories of dealing with health issues?

[Phoebe Marshall]

My first memory of pain was my ankle pain. That was horrible. No one could tell me why that was happening. And it disrupted my sleep a lot. That was really bad.

[Sarah Marshall]

The ankle pain actually started around the time of her sinus infection. And that ankle pain was persistent, really, for years.

[Lauren Bright Pacheco]

What kind of pain are we talking about? Was it just a soreness, an ache?

[Phoebe Marshall]

Just kind of like a dull pain? That's the best way I can explain it. And it got worse with like something over it. I could walk perfectly fine. It wasn't a problem with the bone.

[Lauren Bright Pacheco]

How did that impact you in terms of school and sports and things like that?

[Phoebe Marshall]

Honestly, like, I just kind of powered through as much as I could. No one could do anything. No medication helped. I mean, my pain tolerance was pretty high by the end of it. So it only really, really disrupted my sleep.

[Lauren Bright Pacheco]

I remember that barely five years old, Phoebe was already learning to live with chronic pain and discomfort. Next, her vision starts to fail.

[Phoebe Marshall]

That was hard. As a kindergartner with like an eyepatch.

[Sarah Marshall]

Walking around, she was complaining of black spots in her field of vision. And I myself like sometimes see black spots if you stand up too fast or, you know, blood pressure kind of changes. But then the doctor looked in her eyes, he goes, you know, I think I see something and I'm going to send you to a retinal specialist tomorrow. And then she was diagnosed with retinal vasculitis, where fluid was leaking out of the vessels in the back of her eye. They didn't know why it was happening.

[Phoebe Marshall]

You know, at that age specifically, you see doctors as like literally your heroes. They're supposed to know everything. They are the smartest of the smartest. So when people were like, oh, I don't know, I was like, what do you mean you don't know? I became apparent very young that I was not a cookie cutter case.

[Lauren Bright Pacheco]

In and out of doctors offices, juggling a growing list of strange and seemingly disconnected symptoms, Sarah was increasingly on edge, waiting for the next shoe to drop. She remembers the day it hit the floor vividly.

[Sarah Marshall]

It was a Saturday, it was in the fall and it was a beautiful day. She had been playing outside with the neighbor kids. And I remember thinking that day that this was the first normal day she had had in a while. She really seemed to feel good. And I just remember relishing like what a good day it was. And then that night she said that her tummy hurt and you know, six year old tummy. All the kind of normal mom things that you'd say, have you gone to the bathroom? Do you want me to rub your tummy? Would a heating pad help? And very quickly her pain really ramped up. Within an hour she was laying on my floor just screaming and crying. And in my mind I'm like, we just got back from the hospital, we can't go back. But because I couldn't think of anything else to do, we went to the hospital. I drove her in the car and she was not in her seatbelt. Literally like contorting and writhing and she just clearly could not get comfortable.

[Phoebe Marshall]

I was in so much pain. And I remember saying, I feel like I'm going to die.

[Sarah Marshall]

She thought she was going to die. She said, thank you mom for taking care of me.

[Phoebe Marshall]

And like, no six year old knows that vocab. Like, I work with kids, no kid knows the concept of dying is not in their like hindsight and it wasn't in mine. I remember my mom, she would like keep stopping at red lights. I'm like, I don't know why we're stopping at red lights.

[Sarah Marshall]

I just tried to stay calm. And I said, I'm going as fast as I can. We'll get there soon. We walked in and she was screaming.

[Phoebe Marshall]

I just kept screaming as loud as I was in the car.

[Sarah Marshall]

I don't even know that they asked us our name. We just went back and they immediately gave her Fentanyl and then they gave her Dilaudid and then tried to figure out what was wrong.

[Lauren Bright Pacheco]

I know as a mother there is this exquisite hell of acting like everything's okay when you're afraid that it's not.

[Sarah Marshall]

Oh, yeah. All the time. All the time. And, you know, trying that to cry and lose it myself as my 6 year old is crying and screaming, trying to reassure her that she was going to be okay when I had no idea if really she was going to be okay.

[Lauren Bright Pacheco]

And once you get in to see doctors, they run another set of tests. What did those tests show?

[Sarah Marshall]

Her liver enzymes were sky high. A normal range is somewhere around, say, 30 or 40. Hers were in the thousands. And they started asking me, has she had access to Tylenol? Did she overdose on Tylenol? You know, and so then I'm racking my brain, did she? I don't think she swallowed Tylenol.

[Lauren Bright Pacheco]

Did you get any conclusive answers that day?

[Sarah Marshall]

No. They did admit her because her liver enzymes were so high and her pain was so high. She stayed in the hospital maybe three days and it resolved on its own. It left nearly as quickly as it came on and people just kind of shrugged like we don't know what that was.

[Lauren Bright Pacheco]

Phoebe and Sarah leave the hospital after what feels like a near death experience with no clear direction or understanding of what has happened Again, a few months pass And Phoebe, now 7 years old, starts to indicate to Sarah that her stomach was hurting.

[Sarah Marshall]

It was unremitting, but it wasn't so severe that she was, you know, screaming. But she complained about it daily. They did blood tests, they did an ultrasound, CT scan, MRI, HIDA scan to look at the gallbladder and everything was negative. But she really had this unremitting pain for it was about eight weeks. And finally it was recommended to consult with a surgeon because they said, well, it could be this atypical appendicitis where labs come back normal, but once you go in there, they see kind of an inflamed appendix.

[Lauren Bright Pacheco]

What did they find?

[Sarah Marshall]

They found that her appendix looked great. They still took it out, but they found adhesions. So scar tissue that was actually pretty extensive on the right side of her abdominal cavity. But in particular, scar tissue that was connecting her cecum, which is I believe a part of the large intestine to another part of the large intestine. And so it was pulling. And her surgeon, I remember he came out kind of looking perplexed. He's like, well, this is what I saw. And we lysed them, meaning that they released that scar tissue. And he's like, I don't know why they were there. He said, it looks kind of inflammatory to me, but there's no reason that those should be happening. And we'll just see how she feels after. And she woke up and she had no more abdominal pain. It essentially cured. It cured her pain.

[Lauren Bright Pacheco]

But this cure did not last for long. Six months later, Phoebe presented with the same pain again, and doctors recommended another. Another adhesion surgery. What were you thinking when the conversation about another operation came up?

[Sarah Marshall]

You know, I really hesitated. Do we go in again? Is this. Could this be again, this issue? Because there was no test for these. The scar tissue, you can't see it on any scan. And I'm like, what if her pain is there and there's nothing to see?

[Lauren Bright Pacheco]

So she goes back into surgery. What happened next?

[Sarah Marshall]

He came out and he said, well, they're there again, and they're in the exact same place where they had been six months earlier.

[Phoebe Marshall]

That was basically our routine. Every seven months, I knew the pain every time. Like, once I started feeling it, I was like, mom, call the surgeon. That, like, ruined my life. And I remember thinking like, no one will ever understand.

[Lauren Bright Pacheco]

We'll be right back with Symptomatic A Medical Mystery Podcast.

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[Lauren Bright Pacheco]

Now back to Symptomatic a Medical Mystery podcast. Since she was a baby, Phoebe Marshall has been living with an expanding list of health issues. Infections that escalate to the point of hospitalization, inflammation, joint pain, even vision loss. Her mother, Sarah, has done the best she can while facing constant dismissal from the medical community. Now a recurring surgery to remove adhesions in her abdomen, required twice a year, would become Phoebe's life.

[Phoebe Marshall]

I mean, it was hard to get surgery every seven to eight months. I was carrying around medication in the back at a PICC line. I'd always had stuff hanging from me. There's always a reminder.

[Lauren Bright Pacheco]

So what started as exploratory surgery became maintenance.

[Sarah Marshall]

Yeah, and maintenance for a condition that's not life threatening. She didn't really have a real specific diagnosis. So honestly, no one was particularly concerned about it because it doesn't threaten her life.

[Lauren Bright Pacheco]

Really.

[Sarah Marshall]

I was the only person that was interested in finding a way to never make them happen again.

[Lauren Bright Pacheco]

As a mom, you know, how do you balance prioritizing, finding answers and dealing with these symptoms as they keep coming without letting it take over Phoebe's identity?

[Sarah Marshall]

I don't think I let on to many people how much I thought about what happens when the next thing happens, what will the next thing be? And so I did a lot of nighttime scrolling of the Internet looking for symptoms, matching them to diagnoses, looking for people, for researchers, for doctors across the United States that might have answers that experts where we live, didn't have. But I also think getting her involved in therapy early on was helpful.

[Dr. Jade Rafferty]

My name is Dr. Jade Rafferty. I am a pediatric psychologist. The pediatric part means that I specialize in kids with medical conditions.

[Lauren Bright Pacheco]

Dr. Jade Rafferty is Phoebe's psychologist. Tell me a little bit about your first memory of meeting Phoebe.

[Dr. Jade Rafferty]

So I met her when I was working in pain clinic.

[Sarah Marshall]

She was eight.

[Dr. Jade Rafferty]

So I've known her for a long time, but I don't remember her as much as I remember Sarah. She kept sending messages and she kept attaching these articles that. I gotta be honest, I had no idea what they meant. They were such complex scientific articles that I was like, yeah, I don't know what this means. And unfortunately, and I think it is important to share this, like, I am ashamed that I did contribute to some of that skepticism or had that skepticism when I first met them. You know, like, what is really going on here? I didn't fully understand at that point in my career how complex a brain and body can be. And Phoebe at that time was a closed book. You could not get her to say a whole lot of anything. So I did spend a lot of time sitting there trying to ask her questions.

[Lauren Bright Pacheco]

Sarah remembers this too.

[Sarah Marshall]

She kind of saw Jade as this nosy person that was asking her all these personal questions. And I'm like, well, you know, you can tell her whatever you want to Tell her, like, that's what she's there for. And there was this light that went on, like, oh, I didn't know I could, like, talk to her about things.

[Lauren Bright Pacheco]

What has been the most difficult part for you of growing up with these ever changing, evolving symptoms?

[Phoebe Marshall]

I think a lot of people already struggle with trusting other people, but my medical stuff goes outside of the doctor's office. I have a really hard time trusting other people. Like my friends. I don't open up to my friends a lot. They know I have medical stuff. They know I struggle. But I've been taught over and over that no one wants to hear it. I think also, my story's so complex, it's really hard even to this day. It's really hard to explain to my friends. I remember one time I was in the hospital. It was just after one of my surgeries. I get really weak after my surgeries, and I remember my neurologist ended up coming in to do. I'm gonna get it wrong. An emg. Something where, like, you poke the muscles and you see how tired they get. But he was like, let's just do one now. After surgery to see. And the EMG came back normal. There was nothing really shown there. And I don't think he was like, oh, that means you're faking it. But, like, the look of confusion on his face, like, I wanted so badly just to tell him, like, I. I promise you on everything, I love this is real.

[Lauren Bright Pacheco]

I know Phoebe spoken about how she felt dismissed.

[Sarah Marshall]

Mm. We all did. We all did. You know, it was very, very difficult. And I think I saw the doubt from doctors and, like, what I intuited was that they felt like this family needs help and they need some mental health support.

[Lauren Bright Pacheco]

Though Phoebe's physical symptoms went far beyond the boundaries of mental health and should not have been minimized, Dr. Jade recognizes the emotional impact of what their family was going through.

[Dr. Jade Rafferty]

Well, it impacts the entire family system. We're not taught how to be parents, let alone parents of children with chronic illness. How do we help kids be independent, even if we're having to give them IVs, right? Or how do we help kids go back to school, even if their immune system is compromised? For me, I see it all as health, and I wish and dream that all kids could get mental health care. But then when you add on all of the levels of chronic illness, it impacts and changes how children and their families develop. And that, I think, is really a key component of some of the work that I do.

[Lauren Bright Pacheco]

Now 10 years old, Phoebe has undergone an adhesion surgery every six to eight months for the last four years. These surgeries are invasive, painful, and leave her with extended post operative weakness. Unable to roll over or even hold up her head. Phoebe missed months of school every year as a result. Sarah was unable to accept this as her daughter's continued fate.

[Sarah Marshall]

I was probably the only person whose quest it was to find a way to not do these surgeries anymore because it did impact her quality of life. Who wants to go into surgery once or twice a year and then be in the hospital for a week? I didn't want that for her for so many reasons. She was still having symptoms that weren't in just one organ system. They were across multiple organ systems. And so many of her individual diagnoses were rare in and of themselves. And it's like, how can one person have so many things that are otherwise rare in one short life experience? I was desperate for answers.

[Lauren Bright Pacheco]

In 2017, after years of pounding the pavement in search of answers to their many questions, Sarah came across the Undiagnosed Diseases Network.

[Sarah Marshall]

I found another parent who lived in Wisconsin at the time. And she and her children had just been seen at the udn. And when she told me about the udn, I had never heard of it before. And I thought, we have to go. This is where we'll find answers.

[Lauren Bright Pacheco]

Can you tell me about your first experience with them?

[Sarah Marshall]

So I called the number on their website and a man named Paul answered the phone. And he was wonderful. I spoke to him for about an hour. He listened to my story, he answered my questions, and really was maybe the first time in talking to a complete stranger that was curious and interested and validated that we weren't crazy, that there was hope. He described this program that offered both the clinical and the research component. You know, I had my heart set on making sure that we made it into the study.

[Lauren Bright Pacheco]

And because of Sarah's diligent advocacy, they did. Phoebe and her family then traveled to the nearest UDN research site in Boston. What do you remember about your trip to Boston?

[Phoebe Marshall]

I didn't really understand much about it. There was a pool at the hotel. I was excited for that. But I remember it was a lot of appointments. They had to cram pack all these specialists into one week. I fell asleep at probably more than half of them. And it's a new person examining me, looking at my ears, touching my joints, like, that's a lot for an 8 year old. I remember, God bless my mom. I would get so irritated with her at appointments because I just wanted to Go home. I was so tired. Yeah, that was hard.

[Sarah Marshall]

We went to Boston Children's. They did their clinical evaluation. They took our blood as family and said, you know, we're going to send this off and sequence her exome to see if we could find any genetic possibilities for what's causing all of these symptoms of hers. And then we waited a long time.

[Lauren Bright Pacheco]

Months went by after their trip to Boston as the UDN continued their research. While they waited for results, Phoebe was hit with new persistent back pain.

[Sarah Marshall]

We saw an orthopedic spine surgeon and they said, oh well, she has this thing called Bertolotti syndrome and it's extra bone in your lower spine. And the recommendation that came back was spinal fusion. I was like, that seems kind of extreme. But we tried physical therapy and it didn't really do anything. And so then finally she had spinal fusion.

[Lauren Bright Pacheco]

After the surgery, Phoebe is hit with a horrible post op infection. She is forced to go under five more times in order for doctors to open her up and clean out her wound. When she finally recovers, the pain in her spine is gone. But Sarah is even more desperate for the results from the UDN study. Finally, after an agonizing wait, the UDN shares the results of their initial tests. But the results are not immediately with Sarah has hoped for.

[Sarah Marshall]

So they did exome that came back nothing. But they couldn't tell me and so I was frustrated. What do you mean you can't tell me?

[Lauren Bright Pacheco]

An exome study analyzes the protein coding parts of your DNA. Because the results of the exome study were inconclusive, the UDN decides to run a genome study which examines the entire DNA sequence again. The family waits while they evaluate this more in depth sequencing. But finally, months after they begin this testing, and years after Sarah first noticed something was wrong with Phoebe's health, The team at UDN tells Sarah that there is a mutation.

[Sarah Marshall]

GDF11. It's a loss of function of GDF11.

[Lauren Bright Pacheco]

The first time you remember seeing in print an actual name, an explanation in terms of GDF 11. What did that mean to you?

[Sarah Marshall]

For people that live undiagnosed, it's the dream come true. It's like, oh, this is the name, this is the diagnosis. It's hard to put into words just how, how thrilling it is, you know, to finally have a name. You knew there was something for years and years and years, for over a decade. You knew even when there were so many people, doctors, family members, friends who doubted that really that there was something wrong.

[Phoebe Marshall]

I was 13 at the time. Honestly, I don't think I understood the gravity of it. I wouldn't be where I AM without the UDN and the GDF11 diagnosis.

[Lauren Bright Pacheco]

But GDF11 was a newly identified gene, which means that there was little understanding of how to proceed.

[Sarah Marshall]

Honestly, the feeling was, what next? This is a newly identified gene. It's a newly identified disease, more or less. No one knew anything about it, no one has treatments for it. And so it's this new journey now of what do you do with it? How do you understand these changes and how do you improve the quality of life?

[Lauren Bright Pacheco]

This was the next step in the UDN led research journey. Enter Dr. Hugo Bellin at the Model Organism Screening center at Baylor College of Medicine.

[Dr. Hugo Bellin]

My name is Hugo Belen and I'm a doctor in veterinary medicine and a PhD in genetics.

[Lauren Bright Pacheco]

Dr. Bellin runs the Bellin Lab at Baylor and can be credited with discovering over 60 novel diseases within the genetic research field. Dr. Bellin has been admirably dubbed the Lord of the Flies.

[Dr. Hugo Bellin]

I started working with fruit flies because fruit flies were a superb genetic system, probably the best and still the best system in the sense that you can manipulate flies genetically very elegantly. And that drew me to the field and I've stayed in the field forever.

[Lauren Bright Pacheco]

And how is your work connected to the Undiagnosed Diseases Network?

[Dr. Hugo Bellin]

It turns out that about 80% of the rare disease patients have genetic lesions. The problem is very often that they find potential genes, but they've never been associated with a human disease. They don't know if the gene could be responsible because the gene is not recorded as causing a human disease. So how do you solve that question in this case? For GDF11, there are six patients and we tested these six different variants in fruit flies.

[Lauren Bright Pacheco]

What were the GDF11 research findings?

[Dr. Hugo Bellin]

The GDF11 gene is expressed mostly in muscles as well as in specific cells in the brain, glial cells, as well as in many other organs. And what it is is kind of like a hormone. It's a protein that's made by cells that secreted and it's processed and secreted in the blood and can circulate in fluids, not necessarily just the blood.

[Lauren Bright Pacheco]

And how does that manifest in the body?

[Dr. Hugo Bellin]

For GDF11, morphological deformities are one of the key features in patients. They have bone deformities and they have face problems and their face is not properly developed, sometimes an extra rib. Those are morphological changes in structure. We know that the gene can also cause problems with adherence, tissue adherence in the bone and apparently in the gut. And so because it's such a broad pathway, you know, you can secrete this protein from many sources, and it can bind to ligand to the receptors in many different cells and control the activity and the function of these cells.

[Lauren Bright Pacheco]

The MOSC study, including Dr. Bellin's research, comes out in 2021. And Sarah pores over the research findings, desperately trying to understand if there is any way she can to help find Phoebe some relief. She contacts UDN and requests that they organize a meeting with Dr. Bellin. Do you have any memory of that meeting or your first impressions of Sarah?

[Dr. Hugo Bellin]

Yeah. Sarah has been incredibly active and in a way, proactive. She's been really an advocate for the Undiagnosed Diseases Network because of her experience trying to kind of figure out how she can help her daughter.

[Lauren Bright Pacheco]

Though there was no treatment established for Phoebe's condition at this time, Sarah was not willing to accept that as the final ruling. With the MoSC study in hand, she charged forward.

[Sarah Marshall]

So I listened to a speaker. His name is Matt Meite out of University of Alabama Precision Medicine. And he talked about how understanding gene changes can help medicine understand pathways in people's bodies that might be causing issues. So he talked about a specific example of a kid with epilepsy, and they understood her gene change and came to some ideas for treatments that were not FDA approved for epilepsy, but that they thought might kind of aid that genetic change in that pathway. So I approached him and his staff and told him about Phoebe's gene change at GDF 11. And they took a look at it, and they said, you know, we think that this particular gene influences an inflammatory pathway and that because of her loss of function, that she may have more inflammation in her body than what she should. So we think this drug called Humira, which dampens inflammation, might help with these adhesions.

[Lauren Bright Pacheco]

A drug that already exists, commonly used to target overactive inflammation in patients who suffer from rheumatoid arthritis, may work to address some of the symptoms related to Phoebe's rare and newly identified condition.

[Dr. Hugo Bellin]

And by networking and trying to connect with other teams and by being part of a therapeutics matching committee, she's kind of discovered that there is a drug that helps phobia, and that is this drug that kind of is involved in the immune system. And she was true connections. She's the one who discovered these true connections.

[Lauren Bright Pacheco]

So how has Phoebe's life changed since she made that connection?

[Sarah Marshall]

She has not had one surgery for her adhesions. So in four years. Over four years.

[Lauren Bright Pacheco]

That's incredible.

[Sarah Marshall]

It is incredible.

[Lauren Bright Pacheco]

But you also discovered a treatment because you were so desperate to find relief for your daughter. And Dr. Mom figured that out.

[Sarah Marshall]

Dr. Mom pushed for at least trying something. I think it's really improved her quality of life. This is her fourth year of high school. Since she's been in high school, she hasn't really ben in the hospital. She just wants to be normal and look normal and be a part of the crowd with the kids. And so it's allowed her to do that.

[Phoebe Marshall]

My mom is probably the most impressive woman I've ever met. And I'm not just saying that because she's my mom. Like, genuinely, if she wants something, especially for her kids, she'll get it. I am so lucky to have a mom literally rise at dawn for me. She will do anything for me.

[Lauren Bright Pacheco]

Because of Sarah's tireless advocacy, Phoebe has a bright future ahead of her. While she prepares to head off to college, Sarah, motivated by her own journey, continues to fight for others living with undiagnosed diseases. So tell me a little bit about your work that you do with UDN now.

[Sarah Marshall]

I became a part of this Peer Patient Engagement and Empowerment resource. Our group. This patient group became very involved in the sustainability and interested in the sustainability of the UDN as a resource. So our group, I won't say single handedly, but we had a large voice in a couple of different things. One is connecting with legislators across the country to educate them about the UDN and the importance of the udn and also in establishing a nonprofit called the Undiagnosed Diseases Network Foundation. That is a foundation that was created by patients for patients to support patients and families and also support the quest of finding answers for all undiagnosed patients.

[Phoebe Marshall]

I hear her on phone calls with patients and like, it's not a job to her. She really cares about these people. She cares about the story. She wants them to feel seen because she knows what it feels like to not be seen. And it's important because so many people are undiagnosed. But everyone, kids especially, deserve to have the chance at a good quality of life. And the UDN and UDNF offers people a chance, I think, at life and to see themselves thrive.

[Lauren Bright Pacheco]

A gift that Phoebe herself does not take for granted. What are you most excited for and hopeful about?

[Phoebe Marshall]

Oof. Truly becoming the person I needed when I was a kid and I had so many people. I think being a social worker is kind of my way of giving back to people who believed in me when I couldn't believe in myself. You, you know, I think that's I'm excited for that.

[Sarah Marshall]

In the United states, there are 30 million Americans with a rare disease, and it takes on average seven years to get to a diagnosis. And the cost to individuals, to families, to society is more than it needs to be. And resources like the UDN can shorten that time to a diagnosis that allows people to live their best lives. And that's what we all want. Not only do we want that as mothers and fathers and neighbors and friends, but we want that as a society. We want everyone in society to be able to attend school, to be able to attend work and feel and be productive. And that's why a resource like the UDN is essential.

[Lauren Bright Pacheco]

What is the message you want people to take away from your story?

[Phoebe Marshall]

I've always told myself my thoughts are powerful. I think it's important in the chronic illness world and in just like regular life that you determine the outcome. If you get up every day as hard as it is and continue the fight, surround yourself with people who love you and that you love, there is hope for a better life. My name is Phoebe Marshall and it took 10 years of searching for answers until I got a diagnosis of a loss of function in GDF11.

[Lauren Bright Pacheco]

The Undiagnosed Diseases Network foundation can be found at undf.org as we wrap up another season of Symptomatic, we want to say thank you to all, all of our dedicated listeners. This season brought us stories that remind us of the power of resilience and the impact of advocacy in the rare disease community. We heard from a father who devoted his life to finding a cure for his daughter's condition, from three generations of one family who finally found relief after decades of searching, and from so many others who have transformed their pain into purpose. We can't wait to share more with you next season. As always, we would love to hear from you. Send us your thoughts on this episode or share a medical mystery of your own@ symptomaticheartmedia.com and please rate and review Symptomatic wherever you get your podcasts. We'll see you next time. And until then, be well. Symptomatic A Medical Mystery Podcast is a production of iHeartMedia's Ruby Studio. Our show is hosted by me, Lauren Bright Pacheco. Our executive producers are James Foster, Matt Romano, and myself. Our supervising producers are Ryan Ovadia, Haley Aliyah Erickson, and Daniel Ainsworth. This episode was written by Haley Alia Erickson and edited by Samuel Richards.

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[Frank]

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[Lauren Bright Pacheco]

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[Sarah Marshall]

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