OUR RARE + UNDIAGNOSED STORY
This photo was taken after Luka got a shot of antibiotics after being diagnosed with meningitis at 6 weeks. We were waiting for his first central line placement surgery so that he could get access to intravenous antibiotics as his veins couldn't even hold a peripheral IV due to being over pricked for weeks, weight loss and dehydration. I was happy because he was alert and making eye contact again after going backwards developmentally. This moment marked a lot of tension medically, for being essentially "undiagnosed" brought out strong reactions in different medical providers. Most doctors (the Hem-Onc team) wanted to treat Luka's symptoms, even if they didn't understand why it was happening; yet one provider (on consult from another team) suggested that he was just a "fussy baby." I think we can all agree that Luka wasn't fussy. At all. He was born with a rare and undiagnosed disease that is thought by experts to be unique to him.
This is just one moment of many of what it's like to be undiagnosed. This story focuses on our medical details of our undiagnosed journey, and I could write another 16 pages on the other aspects of disability paperwork, the emotional toll, and lack of access to support and services when not neatly in a diagnosis code.
We are just one family who lives in the reality of undiagnosed, but there are millions of others who face rare disease and don't even have a name for their condition, let alone a treatment plan. Makes me wonder if our nickname for Luka's condition, or "Luki SCID," that we used to joke around about will ever become a reality.
Our rare and undiagnosed story starts on April 15, 2010. Something seemed wrong to me. I was nearly 36 weeks pregnant with our first child, a boy. An ultrasound a couple days prior was normal. The pregnancy couldn't have been more routine. I was 27 years old and the few ultrasounds we had and regular appointments were uneventful. When I called the nurse line telling them that I didn’t feel much movement, the nurse advised that I go to the hospital. The problem was that I was 2 hours away on a brief work trip. A co-worker drove me back while I ate strawberries, and remember telling her that the worst scenario is I will need a c-section. Oh, was I wrong.
My husband didn't know what to do with himself. He had gone to Target and bought shoes, then proceeded to pace for the next few days. For me, I felt still. Figuratively and literally. While our baby wasn't born yet, he already had an identity, a soul, a name: Maksymilian in honor of a Polish saint. He had already flew on a place, ran a 5K and gone paddling on the Haw River.
The moment came when a nurse left the room to get a doctor, who then came in solemnly and upon putting the ultrasound wand to my large, third trimester belly told us, "I'm sorry, but as you can tell, there is no a heartbeat."
I was immediately catapulted into a lightening fast zoom of my life flashing by me. Like in a movie scene right before someone dies and they see their lives flash before them. Yet, this flash for me wasn't linear. It went backwards and forwards at the same time. But the anchor that remained the same was the finality of, "there is no heart beat."
At the time, part of my life flashing by me was the thought, "We'll have another baby." To this day, I cannot believe that this was my first conscious thought after hearing Maks didn't have a heart beat. The rational side of me just wanted to know what happens next, while another side of me felt like my heart stopped beating, too.
We were fortunate enough that the doctor who made this declaration was also someone who researched this very topic of stillborn due to unknown causes. She was also compassionate, even having some similar experiences she shared with us. I don't remember what she said, but I remember how she made me feel -- like we were going to be OK, that this was a terrible thing that happened, that she will search for answers as to why it happened, and to go home and sleep, then return the next morning to induce labor so Maks can be born still.
For some reason my only conscious memory is putting on my sunglasses as I rode down the escalators in the middle lobby of the Women's Hospital -- hiding from anyone who would ask me about my baby in my belly. I didn't know how to even say it out loud. I couldn't even tell my mom and dad -- my husband had to tell them and everyone else. I think that was my way of trying not to admit or accept what had happened.
We returned the next day to the hospital and after about 48 hours of labor, I delivered Maks on April 17, 2010. Instead of a birth certificate, we got a death certificate. He had black hair and was little, but he was perfect. Even the doctors and nurses were surprised. They admitted that often if a baby is born still, after delivery it becomes more obvious what happened to cause the death. But, Maks was perfect. He just did not have a heart beat.
Despite Maks' death, there was a lot of beauty in the process. One of his delivery nurses shared her story with us that included St. Gerard and the mysterious ways in which the spirit can move us, especially when we need help the most. Maks' middle name is Gerard and to this day, we share the St. Gerard medal with everyone we know who has shared a similar experience in the journey of childbirth for St. Gerard is the patron saint of childbirth.
At first, I opted for Maks to have an autopsy to help us understand why his heart stopped beating. Then, all of a sudden the next day, I changed my mind and felt so strongly that I called the medical examiner's office. To this day, I have no idea why I did this. Maybe I didn't want to know the results as it could have changed our future decisions? Maybe I just wanted him to be in peace? Maybe I'll never really know.
Six weeks after, we returned to the same hospital to meet with the same doctor who had pronounced Maks dead. They had taken a lot of blood from me in hopes that some testing would unveil answers to what happened to Maks. Wrong. The only information we walked away with was that my placenta had "infarctions" which may or may not have been associated to a lack of blood flow to the fetus, or may have happened after he passed away. He had spent so much time not alive inside of me that it is hard to know. This appointment was our very first experience of getting back inconclusive test results giving us that feeling like were are disappointed that we don't have a disease. My husband calls it "rooting for disease." It's like our "team" -- or the disease, didn't win. But, did we even want this "team" to win in the first place? The good news is that the testing indicated that I do not have a blood clotting disorder that they are aware of, the bad news is that we still don't know why Maks died. He's undiagnosed today six years after he passed away.
Yet, just like his patron Saint Maksymilian Kolbe a Polish priest who in a WWII concentration camp volunteered to suffer so a family man could survive, our baby Maks was in many ways someone who sacrificed for others. Even though the doctors didn't know why Maks' heart stopped beating, they pointed to a research study recent at the time that had better outcomes (or live births) after a bad outcome (still births) for unknown reasons. That was us. Or at least we hoped it would be. So, per doctors orders, for any future pregnancy, I would give myself a daily injection of a blood thinner in the fat of my stomach. My insurance paid about $1,000 for a monthly dose, and I paid a $100 specialty co-pay out of pocket. The plan also included all that comes with "high risk" pregnancy due to previous bad outcomes (not to be confused with high risk due to advanced maternal age) including more frequent ultrasounds and non-stress tests in the third trimester. I'd also be induced at 37 weeks, as soon as the baby was considered full term.
About 1 year later, on June 6, 2011, I gave birth to a 5 pound baby girl who was smiling as she entered the room full of laughter. She was ready to come, but the doctor wasn't in the room so the nurses were yelling at me to stop pushing. They were paging the doctor over and over again even on the loudspeaker. The thing is that I wasn't pushing, I was laughing at how far we had come -- from Maks to now, but that we couldn't cross the finish line without the doctor. Yet, the laughing created pushing. Once our beloved OB/GYN , who had walked with us the entire journey, came running in smiling that she was right outside the door, our sweet and fun loving Maia was born with a smile on her face. It couldn't have been more opposite of a situation to when her older brother, Maks, came into this world.
Although Maia was small at 5 pounds and needed some help with latching, she was healthy. At every pediatrician's appointment, she gained weight and met milestones. Although she had many ear infections in her first year, a case of chicken pox, and needed a nebulizer from time to time to fight upper respiratory infections, she was perfect in every way. Just a baby in a day care that went to the general pediatrician's office for routine medication and healed, no problem. Maia continued to grow into the lively, free spirited, and happy person she was born to be. We used to marvel how another kid in our family would stand up to her incredible personality, hoping any younger sibling wouldn't always be in her shadow. It's funny how wrong you can be when you make up what you fear to be true. For, in many ways, Maia has been asked to be in the shadows as a sibling.
When Maia was 2 years old and 1 month, we found out we were pregnant and she would be a big sister. At the 9 week doctor appointment, our beloved OB/GYN did a quick ultrasound in the office and on a whim said she's going to order a more in-depth ultrasound at the hospital for dating purposes, just to be sure. We went about 2 weeks later and the ultrasound tech was upbeat and bubbly, telling us everything looks great and bouncing out of the room to have the doctor check the scans. Only for the doctor on call to walk in solemnly, sit down, and take a deep breathe. In a flash, I nearly had a heart attack. I don't remember what he said. Just words like "pregnancy may not be viable," "cystic hygroma," and "genetic testing needed,” and “very, very low chances of a healthy baby, like maybe 5% if you’re lucky.” At the time, I thought 5% sounded like good odds given that Maks died and he seemed healthy all along. (I will note that neither Maks nor Maia had ultrasounds this early in their pregnancies, so we will never know if either of them had a cystic hygroma early in development.)
We were told that there's a simple blood test that can identify if there are any of three genetic conditions that affect the tiny fetus. I had the blood draw, and the tech asked me if this was my first child. If my memory is correct, this was the first time that I gave an accurate answer, telling her, "No, it's my third." As the conversation continued, the tech came to realize that this wasn't a light-hearted conversation with a pregnant mother. It was a set of heavy and loaded questions to me, and that I was facing the possibility of another child dying.
We met with a genetic counselor who I tried to explain that we are sensitive to all of this because of the loss of Maks to unknown reasons. She told me, "lightening can strike twice." Which, while true -- wasn't a comforting thought, at all. We found ourselves continuously caught between this type sentiment and a dismissive approach to our loss with Maks, as if not knowing what happened to cause his heart to stop beating didn't matter to this fetus with a cystic hygroma. As if the only thing in common they have is the same mother and father, which ironically is the basis of genetics.
After that ultrasound appointment, my husband and I went home and laid on the ground. We couldn't move. It was like we were still. As still as Maks. And then it was time to pick up Maia from daycare, and her burst of energy helped propelled us for the next 7 months. She even came with us to a future big ultrasound appointment, for we didn’t have anywhere else for her to go. And in typical Maia fashion, she made it a fun experience, even bringing her favorite stuffed animal, Sneetch, to join us while meeting her "baby brother."
Two weeks later, a genetic counselor called me to tell me that the results were "normal" and that the baby is a boy which you could tell from the test. Although he didn't have the genetic conditions that were tested for, that didn't mean that he didn't have another issue. But what I remember the most from that phone call is being struck that the baby was a boy. For some reason that caused concern in me, perhaps just because of what happened to our other boy. At the time, I didn't remember anything from my last science course in 9th grade biology when we learned about x-linked genetic diseases that a mother can pass to her sons.
So, throughout that pregnancy with our third child who we named Luka, there was one thing after another. Nothing major, but it felt different. I had a hard time eating and felt ill most of the time. I had monthly ultrasounds and the hygroma was resolving, yet I still felt terrible. I continued to give myself the injections and rest as much as I could with a vibrant 2 year old and stressful full time job. During this time, we learned how to truly live one day at a time.
At 37 weeks, on March 4, 2014, Luka was born. I was induced and after 36 hours in labor he came into the world, holding one arm up by his ear, very quietly into a peaceful room. As soon as the baby nurse handed him back to me after she cleaned him up and took some vitals, I asked her if he was OK. I intuitively felt panicked. Her response says with me forever, "He's OK -- as far as we can tell."
Those next two days in the hospital were as normal as they come, but with a few moments that stood out to me. While Luka was very cuddly, he seemed jumpy at the same time. A nurse ran her fingers down his spine and he shirked, nearly jumping out of his skin. She said she'd never seen anything like this before, so she got a doctor to check it out. Of course, Luka didn't do the same thing again. It wouldn't be the first time a medical professional told us that Luka presented information that hadn't been seen before. He got a circumcision, and we went home within 48 hours of delivery.
While Luka slept a lot and didn't have much energy, people thought this was because he was born slightly early at 37 weeks. When we went to the general pediatrician's office for his 3 day check up, he hadn't made up the weight baby's lose after they are born. A couple of days later, he still hadn't gained back the weight. After about a week, he started to get tiny little red spots in his diaper area. At this point, the doctors wanted to see Luka every day for a weight check and were pushing formula. I was even asked by one of the doctors if I was "feeding him" and using the antibiotic ointment on his diaper area like she prescribed. My answer, simply, "Yes. Yes, I am."
Part of the confusion was that Luka hadn't had any fevers, despite this growing skin infection. But, at 17 days old, and nearly every day at the general pediatrician's office, one of the doctors decided to run a simple test, a complete blood count (CBC). So we held Luka down to get access to one of his tiny, dehydrated veins for what was the first of too many to count. The results were confusing. One of the cell lines on the CBC for neutrophils had a 0 next to it. The general pediatrician's office said that they had never seen a 0 before, so it may be a lab error. Normal range for absolute neutrophil count (ANC) is about 1.5-8. They repeated the test the next day, and the result was a 0. We were told to go to NC Children's Hospital and that the Hematology-Oncology department was already on our case. Still, Luka's lack of fever puzzled everyone.
As I carried Luka in my arms from the hospital parking lot to the building, I asked my husband, "Do you think Luka is going to die?" Part of me knew that this is possible, inevitable to all of us, part of me though this question was hyperbole. I marvel at how much I didn't know at that moment in time, for 0 neutrophils should have been the least of our concern.
We quickly learned at the hospital that while Luka had indeed 0 neutrophils, there was a treatment which thankfully was available in the last ten years or so. He could get a G-CSF injection daily that could boost his bone marrow to make neutrophils that would fight infection in his body. Without neutrophils, or a major component of your white blood cells, the body can't get rid of infection which was clearly happening to our newborn Luka. The G-CSF worked and within an hour of the first injection, he was awake and alert. Since he had also developed a severe skin infection in his diaper area, the surgery team was monitoring in case they needed to operate to help it drain. Thankfully, between the G-CSF and oral antibiotics, the rash got better, he started to gain weight, and didn’t need the surgery.
At the time and in a way, it felt like we had all the answers. But, there were hints that we didn't have all the pieces to the puzzle and an expert doctor indicated that Luka will be followed very, very closely to see what happens next. We were told, lovingly, that this was "Luka's story and he is the only one who can write it." This advice continues to carry me to this day.
I did ask the same doctor what the best case and worst case scenarios were, in his opinion. I must have felt comfortable to ask, and the answers were telling, "Best case, this is a fluke and we'll never see each other again. Worst case, he needs a bone marrow transplant." Given Luka's potential for what was called "bone marrow failure," this was always in the back of my mind. My instincts pointed toward the worst, but I was open -- and hoping -- that I was wrong. At that moment, I was committed to during whatever we can -- no stone unturned -- to find out as much as we could about Luka’s disease so that we could carefully consider all treatment options.
During Luka's first hospitalization, I was told by doctors that his condition was so severe that he could not go to daycare and that I should quit my job to be his primary medical caretaker, especially since I was breastfeeding. So that, I did. His big sister also couldn't be in daycare as to avoid the myriad of colds and viruses she could bring home. So, there I was a soon-to-be stay at home mom and nurse to a very sick one month old and a bouncing, and very healthy 2 year old. Not to mention, I had just delivered a baby 4 weeks ago and my body was still recovering. To this day, I don't know how I made it through this time in our lives, but I could also say this about many moments in our lives so far.
After 1 week in the hospital, I hadn't gone outside. I only left Luka's room to tour the UNC Pediatric Hematology-Oncology clinic that we would take Luka to on Mondays and Wednesdays so he could be monitored closely. While we nearly chased Luka's specialist immunologist doctor through the halls, it felt like the rest of the hospital was whizzing by me. Like that feeling when we found out that Maks' heart stopped beating. We even passed those escalators that I rode on with my sunglasses when we were leaving the hospital knowing that Maks wasn't going to be born alive. I was processing the reality that we found ourselves in -- while Luka still had a heart beat, he was very, very sick. Yet the situations couldn’t be more different, both of these boys had the same thing in common -- they were technically undiagnosed.
Because Luka's condition of neutropenia (low neutrophil counts) presented early and severely, it was thought at the time that there could be other issues in his bone marrow and immune system that we would learn more about as his body grew and matured. Since babies have many of their mother's immunity for the first few months and their immune systems are developing, there were many tests that couldn't be done yet. Yet, there were countless tests that had already been run in that first week of hospitalization that I didn't even know were happening -- many different complement tests and other diseases associated with broken or missing immune systems. None of these tests came back conclusive. We didn't know if this was a good thing, or a bad thing.
It was also suspected that Luka had simply "severe congenital neutropenia" (SCN) which sadly, even though a very severe condition, it was relatively speaking for us considered to be "not that bad." In the volumes of diagnostic, genetic tests that Luka had in that first year of his life, this was one of many that came back "inconclusive." In this case, there are several genes with specific mutations have been identified to directly cause SCN. Luka had a mutation in one of these genes, but the mutation was determined not to be the cause of his neutropenia. Rather, the mutation Luka had was different from the standard mutation. But after consult with the researcher who had originally identified the gene, Luka’s unique mutation was determined not to be disease causing. He didn’t have SCN, rather neutropenia as a symptom -- most likely -- of another, more severe primary immunodeficiency disease.
Yet, what remained in Luka's medical chart and social security disability file for the rest of his life, was the diagnosis "neutropenia" when sadly, he didn't have the disease neutropenia. Sometimes resident doctors, early in their career, would come into Luka's hospital room and refer to his condition a "just neutropenia." Most doctors just know about neutropenia as a side effect to chemo during treatment for cancer. Seeing a baby born with this condition was different and not easily understood even for most doctors.
After Luka was discharged from the hospital and his oral antibiotic treatment ended, he stopped tracking, a milestone for babies at around 6 weeks old, lost weight, and was lethargic. Still no fever. He didn't want me to put him down. I remember standing in the UNC Pediatric Hem-Onc Clinic, holding Luka in my arms, and telling his doctor --- who was listening and asked me what I think we should do -- "I don't know what to do, but I know that I'm not leaving here and I'm not taking him home like this." We agreed.
So we stayed on the clinic/hospital campus. Luka got a spinal tap in the ER because of availability and I had to remind everyone that they needed masks and gloves, for he was immunocompromised due to neutropenia. At the time, I couldn't believe that I was the one reminding them. Luka was admitted to the hospital and a wide variety of providers ranging from the floor's resident, the Hem-Onc team division chief, the surgery team, and many nurses came in the room to confirm that Luka's cerebral spinal fluid (CSF) confirmed evidence of meningitis that they were obliged to treat. Since nobody could get a peripheral IV started, he got antibiotics injected into both of his thighs and perked up during that day. The medical team decided to place a central line for access since his veins were so small and still nobody could get an IV started. We had a plan, until a doctor from the infectious diseases team came in and through us off course. A first of several consults from another team that left my head spinning, confused.
This time, and in a round about academic way, the consulting doctor suggested that Luka didn't have meningitis. When I asked him, "If you don't think it's meningitis, then what do you think is going on?" he responded. "You're not going to like hearing this, but babies at 6 weeks are just fussy." Even though me as a mother, his team of experts in immunology, and science couldn't explain Luka's condition -- what we did know is that he wasn't "just a fussy baby." Rather, the opposite for if any of us felt the way he did, I'd bet that we would have been screaming.
So, there we were with a 6 week old baby who had surgery to place a central line to a vein close to his heart so that he could have IV antibiotics and any other infusion he would need at home. By then, I was trained by nursing to both give Luka daily G-CSF shots subcutaneously (in the skin) in his thighs and how to clean the central line caps, dressing, and administer antibiotic infusions using aseptic technique. I remember crying at the pressure and wondering what else will I be asked to do to help Luka stay alive. My husband and I kept procrastinating watching the training video and secretly thought that staying in the hospital would be better than taking care of Luka’s central line at home. Over the next year, we became functional experts in central line care and I miss those days of putting on a mask and putting on sterile gloves.
After another 1 week hospitalization, Luka was discharged and we returned to the UNC Peds Hem-Onc Clinic for his twice a week visits. At this point, he was nearly two months old and doing much better when on daily IV antibiotics. Yet, after the three week IV antibiotics treatment ended, Luka lost weight and got lethargic again. But, still no fever. It started to be a pattern you couldn’t deny. Another spinal tap showed that he didn't have an infection in his spinal fluid nor meningitis, but his doctors’ plan was to stay on these antibiotics as a preventative measure to help him grow and develop, giving us more time to diagnose his overall condition.
What we would find after 12 months of diagnostic tests and treatment of unusual symptoms, is that Luka didn't "just have neutropenia." But, you'd have to know him, us, and his chart very well to get this. During Luka's first few months of life, the antibodies he got from me, his mother, or IgG dropped significantly. During these first few months, Luka struggled with weight gain, mystery rashes, and GI tract issues with unexplained diarrhea. He was referred to a GI specialist and pediatrician who had expertise in "failure to thrive." These experts, while nice, didn't understand much about primary immunodeficiency diseases. They didn't know much about what G-CSF does to other cell lines, not just neutrophils. They thought since the eosinophils were high on the CBC, that perhaps Luka was allergic to something he was eating. But, as as three to four month old baby, he was only drinking breast milk and with a very small supplement of formula. His immunologist doctor, who had been with us since Luka was 19 days old, disagreed and we decided not to take Luka off of breastmilk, especially given the antibodies in IgA that I passed along to Luka through my breastmilk. Turns out, Luka’s eosinophils were high as a result of his G-CSF injections.
Even though just about every genetic test keep coming back negative or inconclusive, Luka continued to present with more and more components of his immune system that weren't working or missing. At just under 5 months, his IgG, which is part of your B cells and also help to fight bacterial and viral infection, had dropped to below the lowest level possible to detect, or less than 135. The normal range for IgG is anywhere from 650-1400 for average, unaffected people. So, Luka started to get monthly (every 3-4 weeks) infusions of IVIG, which is a blood product made from the donations of thousands of plasma donors. I remember Luka's immunologist delivering me this news that he needed IVIG and kindly saying, "I'm sorry." While appreciated his kindness, I told him, "I just want him to have whatever he needs to feel better."
After IVIG, Luka had more energy, reached several milestones quickly like crawling at only 6 months, and had much less diarrhea and not as many mystery rashes. He was even gaining weight which felt like a major milestone. A lot of people in the clinic joked that IVIG is "life juice" and I can see why. I am so grateful that Luka had a team of doctors, lead by an expert immunologist who also happened to be a hematologist and bone marrow transplant doctor. And that this team saw to track his dropping IgG over the course of his first few months of life, turn to IVIG and encourage my breastfeeding -- not discourage it like the GI doctors had. I’m grateful for Luka and my sanity that we had doctors who both knew us well, listened and watched for signs, and made a plan accordingly -- even if they didn’t understand what Luka’s overall condition was exactly. I'm grateful that the team "treated the symptoms" for it gave us a lot of precious time with Luka to see him grow into the unique and wise soul that he is.
We continued Luka's pattern of daily G-CSF injections, daily IV antibiotic infusions at home, and monthly IVIG infusions in the clinic. We went to the clinic twice a week, mainly for labs, to show them the diarrhea, get weight checks, and learn about the next round of diagnostic genetic tests of rare primary immunodeficiency diseases that came back inconclusive. In late September 2014 after a few months of IVIG to give his immune system a boost, Luka's doctors tried again to take him off of IV antibiotics. This time, it went a little bit better than the last two times, but then after a couple of weeks, he was -- yet again -- "off" by losing weight and having less energy. I remember that he had been close to sitting unassisted, but without IV antibiotics, he slowly went backwards and wasn't even trying anymore. Yet, still no fever.
The medical team drew blood cultures and lo and behold, the cultures grew out bacteria indicating a blood infection. Luka had his central line removed, got back on IV antibiotics, and sat up unassisted the next day. The mysterious part was, the bacteria was very difficult to identify and finally about about 10 days, the lab determined it was an extremely obscure and rare bacteria that normally only had grown out in cancer patients who are extremely immunocompromised. Yet, Luka didn't have an immune system because he was born this way -- his body didn’t even have the ability to mount a fever, which is the most obvious sign of how the body fights infection. After getting a new central line, he was discharged and we continued to give him IV antibiotics at home and go back to the clinic for our twice a week visits.
I remember having a conversation in the clinic around this time with another mother who had a baby who was born, unknown at the time, with a rare disease called HLH that didn't activate until his 1 year old immunizations. At the time we met this family, the bubbly 1 year old was post bone marrow transplant, but for some reason the transplant hadn't kicked in yet. She said that when her son when he was a baby, he was a lot like Luka. We shared stories about how they rolled on their sides as very small babies and reached "movement-oriented" milestones early, but could only sleep while being held. On a whim, I told Luka's immunologist about this connection, as he was the primary doctor to both patients. That's when his doctor decided to run another set of diagnostic tests for genes associated with HLH. Luka hadn’t had an immunizations since it was considered a huge risk with his unique condition as a possible way to trigger a bad immune system response such as HLH. It was a long shot at finding a diagnosis, but we all had an intuition that it could lead to more answers. It did.
Little did we know that clues would come from that test, but only weeks later. It was during this October hospitalization that we found out that the lab that did the HLH test wanted more blood -- this time from mother, father, and sister, in order to do more conclusive testing. The team of doctors also did a blood test to match our HLA tissue to see if any of us in Luka's immediate family would be a match for a potential bone marrow transplant. Later, we found that Luka did have a mutation of a gene typically associated with HLH, or the UNC13D gene, but the mutation was considered novel, or never had been seen before. The lab verified this using the family blood samples, and the results have since been verified by several other labs. To this day, it is unknown if this gene is associated with Luka's overall disease.
We enjoyed the next few months of holidays, despite not being able to go many places because of Luka's inability to be in public or around people with colds or viruses. His first family Thanksgiving had to be canceled due to a family member with a cold, and we ate bread at home laughing that we should have gotten a back-up turkey just in case. It was one of the many ways that our life was altered by Luka's unique primary immunodeficiency disease. It was actually one of the only ways that his condition was clear -- what we couldn't do. We couldn’t be in public, at church, in places with too many people. We couldn’t be in the sun, in playground areas with mulch or soil. When Luka got a virus, it was always a mystery of rashes, difficulty sleeping, losing weight, and not knowing what would happen next. Some kids go to the general pediatrician’s office, Luka went to the hospital and Hem-Onc Clinic. At this point in his life, he hadn’t gone more than 7 days without seeing a specialist at the hospital. We knew that hospital campus and parking garage like the backs of our hands and the fastest way to get a spot closest to the pedestrian walking bridge. We had become a professional hospital-going family, and even Maia knew where all the bathrooms, play areas, and elevators were located.
During the holidays, I let go of diagnosis and decided just to enjoy each moment, especially for Christmas which I’m forever grateful for since you never know when it will be your last. Easier said than done, but I was tired. I was tired of waiting. Tired of "rooting for disease" as we called it. Tired of researching the diseases he was being tested for. Tired of not knowing. So I just let go. I had even stopped asking what doctors were even testing him for, as I knew they were going off a list determined by experts in primary immunodeficiency disease. I remember Luka's immunologist showing us a research article that had a list four pages long with all the diseases that Luka's unusual set of symptoms could be. The list ranged from NEMO, to IgM (which he had borderline/inconclusive results with only "slightly" raised IgM), and on and on. Another disease on the list was SCID, or severe combined immunodeficiency disease. While Luka had symptoms of neutropenia and low IgG (also known as hypogammaglobulinemia) that weren't usually associated with SCID, his condition pointed in this direction and his T cells were tested to see if he had SCID. Of course, he had borderline results and some of the testing pointed to "low T cells in some of the sub-categories and low NK cell function," but was not clearly associated with SCID, nor did any of the genes currently identified with SCID place him neatly in that disease diagnosis. That’s not to say that Luka doesn’t necessarily have SCID, as many diseases have new genes identified over the course of years of extensive research. At the time, we were told that Luka could have been something known as "Leaky SCID." Yes, that's a name of a disease. We joked that he had "Luki SCID," as Luki was our family nickname for him. That's when Luka's expert immunologist, in conjunction with other experts in the field, began to explain that although Luka didn't have an overall diagnosis, his disease may indicate that his bone marrow wasn't compatible with life.
One thing that I was guilty of was depending on the online portal for delivering test results, which was random in it’s timing at best. Sometimes the information would come before the next appointment and I didn't know what it meant. I may have driven myself a little crazy by plugging in this way, but what I was doing was searching for any answer at any time. It was as if the lack of diagnosis for Luka was negatively affecting my health, too. So, during that Thanksgiving and Christmas season, I decided to let go of diagnosis.
After the new year, we all doubled down with pushing for a more comprehensive way of diagnosing Luka's overall condition. All these one off diagnostic genetic tests at different labs across the country were not only taking up a lot of time, but were also expensive. We were fortunate enough to have incredible health insurance through my husband's employer and financial support from the hospital that treated Luka, as well as from family members. But, someone was paying for all these tests and there had to be a better way. Luka's immunologist wanted to do whole exome sequencing that would comb through all of the 20,000 known genes to determine if Luka had mutations (changes) that are typically associated with disease. While Luka's doctor didn't promise anything conclusive, it was the right path to go down so that we could have as much information as possible -- even if that information wasn't conclusive. I remember a representative from the insurance company even telling me that most people who have whole exome sequencing don't get answers and to prepare myself for this. I thanked her for her honesty and told her that we need to do it, no matter if it's conclusive or not.
I'm sure Luka's doctors and social workers completed extensive paperwork for all these tests, and especially for the whole exome sequencing. I bet they could write an even longer book with their point of view. And while whole exome sequencing wasn't entirely conclusive, it did produce interesting results that could inform science, at some point in the future. And, in my opinion, at least we tried and we won't live wondering "what if." In addition to identifying the MUNC-13 (UNC13D) gene with a novel heterozygous mutation, the sequencing also identified the following additional three heterozygous mutations (alterations):
CFH c.2084C>T (p.P695L)
DOCK8 c.3010C>T (p.R1004W)
UNC13D c.547G>A (p.V1831)
We got these results right before Luka’s 1st birthday. It felt like a victory, even though we still didn’t have a diagnosis for this unique combination of gene mutations still didn’t fit into any currently known diagnosis. All that was known is what types of diseases these genes are typically associated with: primary immunodeficiency, HLH, inflammatory diseases, autoimmune disorders, and so on. We had done nearly everything we could do to find a diagnosis, and many doctors say we just don’t have a diagnosis “yet.” And, another way to look at it is -- there are only 20,000 genes that have been identified, and some diseases may be associated with genes that haven’t even been found yet. When we met with a genetic pediatrician, this was her biggest soapbox -- the notion of “yet.”
We were also fortunate enough for Luka’s grandmother to work at the NIH Clinical Center and experts there were willing to analyze these whole exome sequencing results, only the find the same information. As was the same for experts at Cincinnati Children’s, another international leader in primary immunodeficiency diseases and undiagnosed conditions. This gave us three independent institutions coming to the same conclusion, that Luka’s disease may be unique to him and that it doesn’t fit into any current diagnosis. To this day, Luka is still considered undiagnosed, yet when you look at his medical file the first symptom of “neutropenia” is in the first diagnosis code. If only it were “just” neutropenia. Another line in the diagnosis code is “disease of the white blood cells.” I wish it were that simple, too.
So, after 12 months of enduring a disease that may be unique to him, Luka’s team of doctors declared that his “bone marrow was not compatible with life” and that he needed a bone marrow transplant for treatment in order to have a chance. Although none of us in Luka’s immediate family were matches for a bone marrow transplant, the international registry yielded several potential options. We were now with a different waiting game to see what would happen with all the steps needed to get to the actual transplant. There were a million questions -- would the donor pass all the screening tests, would he or she agree, would it work? Again, only time would tell and this was, of course, Luka’s story.
At this point, Luka was just over a year old and we took our first out of state trip with him to visit his grandparents by car. It was medically OK’ed, but I had a feeling that we wouldn’t be able to last a week without being seen by a doctor, for usually things started to go south right when it was least convenient. But, we lasted all week, only to return home and things weren’t right. Of course, Luka didn’t have a fever -- never did - but he was off. I had gotten in tune with Luka’s unique signs that something wasn’t right, for even though he was considered “ahead” in many developmental milestones, he always went backwards when we was sick relative to his usual ability level. This time, Luka wasn’t walking as much and sleeping a lot more. You could also tell in his bowel movements that something wasn’t right as well as with his mystery rash. But, in typical Luka fashion, if you looked at him, you would “never know” as many neighbors, doctors, and nurses would say. By now, I had learned the best way to describe symptoms to doctors and nurses, and to always reaffirm at the ending what I knew they were thinking, “But, he looks great! He always does -- don’t let that fool you.”
After some blood cultures, it came back that he had a fungal infection in the blood. Back in the hospital, but this time with some reassurance that the bone marrow transplant process was underway, both on the health insurance and the actual donor side, and that we had done all we can do to search for a diagnosis with the whole exome sequencing and getting other experts across the country involved. This time, Luka’s fungal infection was also mysterious, rare, and essentially obsolete except for a few cases written in a journal of patients who were severely immunocompromised post bone marrow transplant. It took two weeks for the lab to identify this unusual fungus, and by then his team had decided not to remove his central line. After reading the article about how this fungus had presented and the outcomes, I shared it with Luka’s immunologist and within 24 hours the central line was removed and then shortly after a new one placed.
This central line removal and placement surgery combination was one that us and Luka would become intimately knowledgeable about, with 11 surgeries of this type in Luka’s lifetime. We’ve met every pediatric surgeon at the hospital. We’ve had a minor complication that landed us in the Pediatric Intensive Care Unit (PICU) for a one night preventative stay, we’ve even developed a “breakfast regular” in the hospital cafeteria to eat on the mornings while we waited for the surgery to finish. We’ve debated with doctors when Luka would be NPO (nothing by mouth) before the surgery, some thought no breastmilk 4 hours prior, while others would say 2 hours. Trust me, those extra 2 hours meant a lot to a hungry baby and breastfeeding mother.
After this fungal infection, Luka got on a daily IV antifungal regimen and I gave it to him just like I had been giving him his daily IV antibiotics via his central line at home every day. The UNC home health delivery crew that brought us these weekly boxes became our friends, as we saw them once a week and they always loved seeing Maia and Luka run to the door for the next box. At this point, I was used to it all. I was just happy that Luka was alive, that the bone marrow transplant was upon us, but I didn’t know how much energy I would have for the 6 week plus hospitalization for Luka to get his bone marrow transplant. Little did I know that this stage of the triathlon would not be the hardest, at all.
What I did know is that Luka couldn’t live propped up on IV antibiotics and antifungals, and now twice a week G-CSF injections, especially not knowing the origins of his disease or how this would manifest over time. It was better to have a bone marrow transplant sooner, than when it all got much, much worse. His doctors agreed and the fungal infection just emphasized this point even more.
In all the preparation for transplant, the extra labs drawn, or maybe something else, Luka’s red blood cells dropped and he needed a transfusion. I remember my stomach turning just seeing the red blood in the clear tubing. Which now makes me laugh now since it was the first of many, many blood transfusions and I could practically do it myself at this point.
On June 17, 2015, Luka was admitted to the hospital to get a second central line placed so that he would have three access points in total for all the infusions he would need for his bone marrow transplant. He would get two weeks of chemo as preparation regime and then the actual stem cells from the donor's bone marrow during a rather un-eventful inusion around July 3, 2015.
To prepare, Maia had her birthday party a couple of weeks early, we went to the beach for a weekend and let Luka play in the sand, and we tried to live as normally as possible with Luka and I even dropping Maia off for her first day of summer camp and took a quick trip to the grocery store with the two of them thrilled at the opportunity to ride in the race car shopping cart together -- an unusual treat since typically Luka wasn’t support to be out in public as any virus could potentially delay transplant. Two days later we’d move into the hospital. I was trying to get everything ready and was in such a hurry the day before Luka’s admit date that I put my cell phone in the laundry. Every moment living up to transplant felt like prepping for a life-changing event, yet we didn’t really know how much life would actually change.
Our undiagnosed story doesn’t end here at the beginning of the conditioning regime of three different kinds of chemo to prep for transplant, but in many ways it just begins. While Luka handled the actual bone marrow transplant process fairly well, he did have engraftment syndrome shortly after transplant that led to rashes, high fevers, and was just overall miserable. He needed a lot of steroids to help the inflammation go down, and this may have been a hint that there was trouble to come. While Luka handled chemo fairly well despite some reactions needing benedryl and steroids, it was all the side effects that caught up to him post transplant.
After we were discharged at the end of July after 6 weeks in the hospital, Luka seemed OK only to get the EBV virus (commonly known as mono) matched with mixed chimerism, meaning that his cells and the donor cells were mixed up and he wasn’t quite at 100% donor cells. He developed a blood infection and needed his lines removed and was replaced with a more temporary PICC line, only for that to develop a blood clot matched with very low platelet count. He got rituximab infusions twice a week to fight the EBV and after 5 weeks of this treatment, he finally had no trace of EBV in his blood. During that time, Luka needed constant platelets and red blood transfusions, and the chimerism wasn’t getting any better. But, he “looked great.” It was incredible. It made us all shake our heads. We spent nearly every weekday in the clinic getting 5 hour plus long infusions, watching PBS kids, and delighting all the nurses and doctors with Luka running around the clinic.
It was only until the next week, Luka started to get waves of his body temperature rising once a day. He seemed a little off, but it was subtle. He was on about 13 different medications and it was often hard to know if it was all just a side effect from the medications and treatment. One Sunday morning, Luka woke up and really just wanted to crawl into my lap and not play. I knew something was wrong and his temperature revealed it was above the threshold to go to the ER per post bone marrow transplant protocol. There we were, this the fourth time we’d be at the ER unexpectedly, not realizing it was the last. I remember telling an ER resident that if Luka didn’t have a blood infection, then I’m worried what it is. He agreed.
Sadly, I was right. It wasn’t a blood infection, and it took 1 week to end find out that Luka had the HHV6 virus in both his blood and spinal fluid. He went into respiratory distress and had to have a rapid response to take him to the Pediatric Intensive Care Unit (PICU). There, he got oxygen, more steroids to better protect his brain, and an NG tube to drain his enlarged stomach. It was by far the worst Luka had ever been. All those times he was hospitalized and “you’d never know,” when treatment would make him perk up seemingly in hours -- that wasn’t happening. This time, Luka couldn’t talk, he couldn’t walk, and he could barely even lay on me or lay down in his crib to get comfortable. There were times when I felt like we were praying for a miracle.
The next two months were the hardest of our lives. Yet, I had no idea how bad it would be until it was all over. Instead of Maks’ heartbeat stopping and us finding out in an instant, Luka’s death would be a battle that would last 48 days in the hospital with no end in sight. One of those last days, an overnight resident who didn’t know us and didn’t have the ingrained compassion perhaps needed for Hem-Onc, uttered to me, “I just don’t know where this is going.”
Deep down, we all knew this -- yet we just didn’t say it out loud. For nearly everyone on the Hem-Onc/BMT team -- doctors, nurses, child life specialists, chaplains, social workers, physical therapists -- had all come to know and adore Luka. They were part of The Pride, Luka's circle of love that extended family, friends, and health care providers. They had seen him grow from a newborn to a toddler, from just laying in his crib to walking around his room, from sitting in a bouncy chair to being pushed around in a car toy. They had watched Luka grow up and were just as taken aback that after two grueling months of rigorous IVIG infusions every other day, all the anti-virals his body could take, too many blood and platelet transfusions that you can count -- Luka’s body just couldn’t take it the HHV6 virus anymore. It was in his blood, spinal fluid, and stool. Anytime it would get better or come back, his body would become inflamed spiking high fevers, rashes, and extreme discomfort, and then the virus would be back.
Luka’s doctors tried to get him into clinical trials for new drugs and new treatments, but nothing worked or he was too sick to be a candidate. His body just couldn’t control what experts called “cytokines release syndrome” and even after tocilizumab infusions, it would help and then all come flooding back again. Shortly after Thanksgiving 2015, Luka’s organs began to shut down and within 48 hours he passed away peacefully with his mother and father laying down next to him, holding his hands. We opted against a surgery that could have easily ended his life on the operating table and just prolong the inevitable. All doctors in the PICU and the Hem-Onc/BMT team agreed. It was best for Luka to go in peace, and surrounded by support and love from family, friends, and his medical team, whom we affectionately call The Pride, in a circle of love.
Luka is still undiagnosed. A lab at Cincinnati Children’s has his original stem cells that they can test to better understand the origins of his unique disease. For now, they just know that in a lab setting, his bone marrow doesn’t produce neutrophils, yet with G-CSF they do. They don’t know why. Yet.
While Luka isn’t on a patient registry, we plan on helping his doctors put him on one.
And while we still don’t have answers to Luka’s overall undiagnosed condition, we feel strongly about helping others who face rare disease and find themselves in a similar position, especially patients and families who don’t have the fortune of having a doctor with expertise stand next to them their entire journey and go the extra mile to find whole exome sequencing and other treatments that can give the patient a chance. Nobody should ever be alone, but certainly nobody with who is undiagnosed and already facing the isolation of not having answers.
That’s why to honor Luka, we’ve started the Luka The Lion Foundation to support kids with rare diseases and their families so nobody ever feels alone. We’re honoring Luka’s spirit as a lion, as he taught us to always remember to roar by showing us how he embodied the characteristics of a lion: beauty, bravery, strength, and resilience.
We’re still searching for a diagnosis and what Maks and Luka’s conditions may or may not teach us about science, genetics, and our family. We still don’t even know if their conditions are connected -- we don’t have proof that they are connected, and we don’t have proof that they are not connected. We’re still finding balance between these two extremes -- it’s s the very notion of what it’s like to live in a family that braves undiagnosed diseases.
For us, especially for Maks and Luka, undiagnosed is a diagnosis. The story isn’t finished. Yet.
- Julia Fisher | Founder | Luka The Lion Foundation