Symptomatic: A Medical Mystery Podcast

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

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).

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])

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])

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

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])

More information:

• Undiagnosed Diseases Network Foundation: undf.org