Ode to Fiona: The Face of Fortitude in FBXL4 Deficiency

Abstract

There are some moments in medicine that stay with you forever—putting on your white coat as a medical student for the first time, experiencing the sorrow of disclosing a terminal diagnosis, and the joy of seeing a newborn in her mother's arms after delivery. One of those indelible moments for me is the moment Fiona took her last breath, and experiencing her mother's pain as if it were something tangible in the room.

I met Fiona when she was just 4 months old, when she was intubated and sedated in the PICU in the throes of influenza. I noticed how small she was; her little hands laid inert at her sides. She was more sick than typical, even for influenza, with a lactate level amongst the highest I had ever seen. I did not know what her diagnosis would be, but I worried it was not going to be good.

A few days after I met her, we had our answer for why Fiona was so ill. She had two pathogenic variants in FBXL4—consistent with FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome. We corralled the PICU team and her parents for a meeting. In an austere PICU conference room, we laid out the news. In retrospect, it was one of the last family meetings we would have without masks on. I struggled with the variability of the prognosis—I had cared for a 10-year-old with the condition, but the literature reports a median age of death of 2 years. Fiona's parents were devastated with the news—that combination of shock, sadness, and uncertainty laid out on their faces and in their words. Through their tears, they also expressed hope—they told us Fiona would be a fighter.

Fiona did indeed fight and impressed us all with the speed of her recovery. Within a few weeks, she was well enough to go home. Fiona was 5 months old, and it was March 2020.

Fiona's family's life changed right as the world changed amidst the COVID-19 pandemic. Our first follow-up visit was one of my first virtual visits. Instead of that sick, pale baby lying on a bed, I was on screen with a smiling baby at home in a bouncer. We chatted about her health and the unpredictability of the future. There were so many practical matters to consider which changed the way I thought about her care—was it worth risking exposure to COVID to send her to the lab? She would benefit from therapies, but would it be safe to have those providers in the home?

At our visit when Fiona was 6 months of age, some of my own fears about her prognosis were dispelled. She was rolling! She laughed and she babbled. She loved playing with her big siblings. Aside from some mild delays, I would not have had any idea she was affected with a mitochondrial disease. At 15 months she was trying to crawl, and sometimes saying “mama.” At each visit, I shared in Fiona's mother's joy at her progress.

In May 2021 things took a turn for the worse. Fiona was sick; the sickest she had been since the hospital stay when we met. A choking episode led to aspiration, respiratory failure and intubation. One of our fellows texted me—would I be able to come see the family? I was 40 weeks and 2 days pregnant, but I needed to see her before I delivered. I rode the elevator to the PICU with my hands on my gravid belly, seeking calm and hope from my daughter's kicks. Fiona was lying flat on the hospital bed—so pale, small, and listless—while the ventilator kept a steady pace in the background and three pressors hung from her IV pole. I hugged her mother as she cried and shed tears of my own. “Is this the end?” her mom asked. I wanted so desperately to reassure her, to say something encouraging. I pictured Fiona rolling into my clinic in her wagon, smiling broadly and dressed in outfits coordinated from head to toe. I remembered her mother's pride in sharing new developmental milestones at each visit. That day I stood with Fiona's mother, about to join her in the journey of motherhood, and shared her fear of the unknown.

A few days later with my own healthy newborn beside me I could not help myself from checking in Fiona's chart—I sighed with relief that she was still alive. I thought about how lucky I was to be taking my baby home while Fiona was still in the ICU. Fiona recovered within a few weeks and made it home for an uneventful summer (Figure 1).

In January 2022, my pager went off unexpectedly on a cold, bright Saturday winter morning. It was my colleague on-call, asking me to call her about Fiona. She told me Fiona was admitted with some viral symptoms and had arrested. The team did compressions, and her circulation was restored, but she was unstable even on the ventilator. Did I want to go in to see her? I turned the shower on as I was hanging up the phone, and dressed as quickly as I could. I gave my 7-month-old daughter a hug while she smiled at me; she had no idea that my heart was breaking for someone else's baby. My wet hair froze a bit on my walk to the car, and I drove to the hospital with tears in my eyes and a pit in my stomach.

I got to Fiona's room in the PICU and realized—oh—it was her time right now. I hugged her parents and stepped aside. The room was full—doctors, nurses, Fiona, and her parents—but quiet and calm. Fiona looked peaceful in her hospital bed. Her blonde hair had grown almost to her shoulders, and her blue eyes were shut. Over the short 2 years and 3 months of her life she had lost her round baby cheeks and was becoming a lean toddler. The child life specialist was softly playing her acoustic guitar and singing Fiona's favorite songs. I can vividly picture hearing the lyrics to Katy Perry's “Firework,” “Do you ever feel, like a plastic bag, drifting through the wind, wanting to start again?” as the nurse prepared to remove Fiona from the ventilator. I thought about Fiona's life, and how she was a firework of her own—a spark and a light to everyone who met her.

There was a stillness as Fiona was extubated. She was cradled in her mother's arms, looking like she was just about to lay down for a nap. We all bore witness as Fiona took her last breaths. She stilled, and her mother let out a cry that still echoes in my soul—a cry of anguish, despair, and unfathomable loss. My heart raced as my own tears fell, and grief hit me like a cold plunge.

In that moment, I realized that something had changed in me as a doctor when I became a mother. I expected that by becoming a parent I would have more practical advice for families and more “hands on” experience with children. I did not expect a change in my emotional relationship with the job that I had been doing for many years. I had seen death before but the true horror of losing a child had never been so real for me. I now see echoes of myself in parents receiving bad news; I see similarities to my daughters in the children I care for. Empathy has taken on a whole new meaning that I did not know existed until I first held my daughter after her birth. I think of Fiona regularly as my daughters continue to grow and experience things that Fiona never could. I think of Fiona's mother—her loss and her strength—especially on those cold and bright winter days.

In my experience, geneticists do not always talk about how becoming a parent alters the way we approach our work. From the moment I felt those first kicks in my belly, I anticipated a bright future for my daughter. Yet at work I might have to go tell another family their child would never learn to walk or talk, or that their child would eventually go blind. Those conversations feel completely different now when I see parents' grief, and I mourn for them more than ever before. I understand how sleep deprivation and wildly fluctuating hormones in the postpartum period make day-to-day life a challenge, and yet some mothers experience that tumultuous time while sleeping on a chair in the NICU next to their ill babies. I see the resilience and dedication parents have when they take their children to countless doctor and therapy appointments. Becoming a parent, and caring for Fiona in the process, has deepened my empathy. I am not sure if patients or their families would notice the difference, but I notice it when I carry their emotions, fears, and hopes home with me at the end of the day.

The television adaptation of Emily St. John Mandel's “Station Eleven” has a quote that has always stuck with me. One character, a doctor, tells another what the profession takes—“The courage to bear witness to death is the job, the courage to be there.” Sometimes I find as geneticists we can provide life-altering treatments, but other times we are the ones to bear witness with these families: to their suffering, but also their joys. I am grateful I was able to bear witness, as a physician and a mother, to the life of Fiona and the joy and spark she brought in her short time here.

Dr. Amanda Barone Pritchard conceptualized and wrote this work.

Informed consent has been obtained from the patient's family, including consent for publication of photographs.

The author declares no conflicts of interest.