The quest for a diagnosis has been a recurrent theme in my daughter’s life. She is 21 now, legally an adult, but she will forever be a woman-child. I knew something was wrong with Emily when she was an infant. She was difficult to feed as an infant, never babbled or cooed, did not make her needs known – even as an infant. She had had what her pediatricians at the time termed “a hard time” so she never quite caught up. She had indeed had a hard time. She was admitted to the local hospital numerous times as an infant for failure to thrive/dehydration/diarrhea. The last admission only because I was so stressed, sleep deprived, and at the end of my rope that I practically shouted at the pediatrician in the Emergency Room of the New Jersey hospital where I worked as a critical care/telemetry nurse. They were going to discharge her home again, with bloody diarrhea, dehydration, anemia, and a refusal to nurse/take a bottle. She was not quite 3 months old. She spent a total of about 8 weeks in the hospital this time. She was transferred at my insistence to St. Christopher’s Pediatric Hospital in Philadelphia, where she was cared for by a team led by a pediatric GI specialist (Dr. Jonathon Flick). She had a colonoscopy done, a PICC line placed, a blood transfusion (on Thanksgiving Day), and TPN (total parenteral nutrition) started. She was no allowed anything by mouth. The team determined that she had an allergy to milk and soy protein. She would need a special formula, Neocate. It would need to be drop shipped from a medical specialty pharmacy. The cost was astronomical for a single mom. Thankfully, my medical insurance agreed to cover the cost, the option would have been for me to pay out of pocket which would have bankrupted me (I had 2 other children), or place her in a pediatric facility so that she could continue to receive TPN via her PICC line rather than formula by mouth. Days consisted of my leaving the hospital at 6 am to get to work by 7 am. My father, who was retired, would trek over from NJ and spend most of the day with her. I would return each night around 4 or 4:30, sometimes my dad would still be there, other times he would have headed home – leaving me a note about their day together. It was rough, but we had a diagnosis and a solution. I became a label reading maniac. It was very difficult to find baby food that did not contain milk or some form of soy. I resorted to making my own. It was safer. She came home about two weeks before her first Christmas, she was 4 months old. Diagnosis: milk/soy allergy, dehydration, failure to thrive.
At age 2, she still wasn’t talking. We saw a neurologist at ST. Chris’ and had a BAER hearing test and an MRI of her brain done. Her hearing was perfect, her brain however, showed some abnormalities. She had periventricular leukomalacia, basically she didn’t have enough white matter to transmit her brain signals well. They also say something that they called a mega cisterna magna. The cisterna magna is where the cerebellum sits, her cerebellum is underdeveloped, so the area that houses it is larger looking than “normal”. The neurologist lacked enthusiasm for trying to figure out why she still didn’t speak, she wasn’t convinced that her brain abnormality was the cause. We learned how to do some basic sign language and that helped me figure out what she needed. Her favorite sign was “more”.
Fast forward to age 3, and another admission, this time much, much worse. I woke her up to go to the babysitter’s house and she still had a fever, the same fever her dad had returned her home with the night before. This morning’s fever was accompanied by an inability to stand up unaided. I treated her fever, but because it was well beyond the time that I could call out for my shift (for a 7 am shift, you had to call out by 5 am), I had to go to work. As a single mom, I could not afford to lose my job. I dropped her at the sitter and told the sitter that I was going to get someone to work for me and come back for her. I spoke with my nurse manager and explained that I needed to leave for a sick child, then I called my neurology friend to get his advice on the dizziness and fever. He thought that it was likely a virus affecting her inner ear, but I could call back if things were worse or I was still concerned. I called the sitter to check on her and she was out of it, had not eaten and they could not get her to drink. I spoke with my nurse manager again; they were finally able to get me a replacement. I called the pediatrician’s office, using he super-secret number one of the billing ladies gave me after I cared for her mom in the hospital (it was difficult to get past the front desk staff to speak with the doctor). I spoke with him and was told to being her in the side door, do not enter the waiting room. By the time I got her there she was rousable, but deteriorating quickly. I had to go to the ER and she would need a lumbar puncture. I immediately called my neurologist friend back and asked him to meet us there to perform the lumbar puncture. The pediatrician was not happy with me, they want the neonatologist to perform the LP, however I didn’t have a lot of confidence in her as a physician, so I didn’t want her performing the procedure. He agreed to meet us there and he did her LP, I was in the room. The cerebrospinal fluid was cloudy on inspection. A dose of IV steroids was administered STAT. The next time anyone from the nursing staff entered the room, they were wearing isolation equipment (gloves, gown, masks, booties). She had bacterial meningitis, she needed to be transferred again. We went back to St. Christoper’s in Philadelphia. My boys had to once again stay with the sitter…THE SITTER!!! Oh NO! I dropped a baby with meningitis off at the SITTER’S HOUSE!!! With all the other BABIES!!!!!! Thankfully it was not Neisseria meningitidus, she had Haemophilus meningitis a form of bacterial meningitis caused by the Haemophilus influenzae bacteria. It is usually (but not always) associated with Haemophilus influenzae type b. The other children were all ok, my sitter had numerous conversations with my pediatrician regarding transmission. She spent a week/10 days in the ICU before being moved to a regular room and then discharged 4 days later. Most of her time in the ICU was spent unresponsive, and receiving antibiotics. I stayed with her the entire time she was in ICU and then went back to work during the day and spent the nights with her at the hospital. No one relieved me this time, my parents only visited once because my mom was too upset. They discovered that her immune system was not functioning the way that it should be. Tests for spina bifida and HIV were run, both were negative, she did not have titers to any of her childhood immunizations either. We were discharged with a referral to see an immunologist and a hearing test. It turns out that even though she was given steroid immediately, she still lost complete hearing in her right ear. Diagnosis: Meningitis, immunodeficiency; hard of hearing, deaf in the right ear.
Another quest for a diagnosis. The immunologist took a very detailed history. There were numerous blood tests run, one of the blood tests cost over $2,000.00! After looking at the blood test results (she had no titers to any of her childhood immunizations), and going over her history (Emily had a bout of pneumonia, chronic sinusitis, skin infections all before age 3) and physical examination, they determined that she had hypogammaglobulinemia and would need monthly intravenous (IV) injections of gammaglobulin (IVIG). IVIG is a blood product pooled from multiple donors. It carries the same risks as receiving a blood transfusion. Her first two infusions were done in the hospital; the remaining infusions were done in our home by a home infusion company. Prior to the start of her IVIG infusions we had an appointment set up for Emily to have sinus surgery to drain her chronically impacted sinuses. The immunologist did not think that the IVIG would clear her sinuses, however, after the first infusion, she no longer had that thick green discharge from her nose. We did a quick MRI and overnighted the results to the Ear nose and throat doc who agreed that surgery would not be necessary. The IVIG cleared her sinuses up! The docs figure that it was the chronically impacted sinuses and an immune system that did not function well that ultimately led to her meningitis. Diagnosis: hypogammaglobulinemia
When Emily still wasn’t talking well at age 3, was clearly delayed in her gross motor development, the pediatrician wanted to send her to a geneticist. The geneticist took a comprehensive history and ordered additional blood work. The blood work showed that she was missing a piece of chromosome 3q. There was no additional information. I was tested, her father refused to be tested. My test was negative. Because the FISH testing was so new (at that time), no one knew what the results meant. There was no follow up testing done. After we saw the geneticist, the neurologist was up next. I did not like the first neurologist who tested her hearing and ordered the MRI of her brain, so I got some referrals and did some digging around to find someone new (this all occurred before Google). I found a wonderful neurologist in Delaware, affiliated with Dupont Hospital for Children. I brought the blood test results that were done and her MRI. He took one look at her MRI and asked if I minded whether he showed it to his partner. I agreed, he then told me that he never saw an MRI like hers. Not something a parent wants to hear. As I explained above, I knew her MRI was abnormal. My complaint was lack of speech, and global delays in motor development. He said that according to her MRI, she probably should not be able to walk. He explained that as far as her language went, the information can enter the brain (she can understand), but there is a delay in the output (language). The fact that she can sign is good. He also diagnosed her with PDD NOS (pervasive development disorder not otherwise specified). At that time, he described it as her “borrowing” traits from the autistic community without being autistic. OK…clear as mud. I did some research and spoke with a lot of people about PDD and was basically told that it was an “umbrella” term to catch kids with delays but that don’t have a hard diagnosis. It wasn’t until she was in middle school that I went and researched the term again and discovered that it is now considered an autism spectrum disorder! All I could think about was all that wasted time…time when she could have been provided therapy was gone. We had followed up yearly with the neurologist but stopped seeing him right before middle school. We did reconnect when Emily was a senior in high school. He was amazed at her progress, I brought the old MRI, and a newer one with me to remind him. We talked a lot about the PDD diagnosis and what the future might hold for Emily. Her diagnosis was no longer PDD, because the DSM was about to change, she was now considered to have an autism spectrum disorder. He suggested that we apply for guardianship when she turns 18. Diagnosis: PDD NOS; Autism Spectrum Disorder (ASD)
In 2009, after Emily having some dysplastic moles removed, I was looking on ClinicalTrials.gov to see if there were clinical trials available for dysplastic nevus syndrome, when I stumbled across a study (observational) for people/kids with undiagnosed syndromes at the NIH (National Institute of Health) in Bethesda, MD. I had always thought that there was more going on with Emily than just what we knew and often wondered if she had a syndrome of some sort. I e-mailed the contact and described Emily. The response was to schedule her for an appointment to see the staff at NIH. This would be an all day appointment. She would meet with the staff in the Undiagnosed Syndrome Clinic. There was an extensive history taken, honestly it is like living in a fish bowl, you are constantly being compared to “normal” and little things like the height of your ears, or thickness of your lips are constantly being assessed. The physician was sure she had one of two chromosome deletions…we needed more blood work for a definitive diagnosis. Diagnosis: 3q29 deletion syndrome.
Emily began having lower quadrant pain around age 17, and was experiencing prolonged and painful menstruation. I made an appointment for her with my gynecologist. She met with Emily and asked her some questions, most of them Emily could answer but deferred to me for many of them (autism spectrum disorder). A decision was made to try low dose contraceptives to shorten the length of her periods, and decrease the amount of bleeding. Her pills were to be used continuously. We were also sent for an ultrasound of her abdomen because of the abdominal pain. Diagnosis: Ovarian Cyst
About 6 months to a year later, Emily began having lower quadrant pain again, but now it was to the point that she felt unable to go to work. I called the gynecologist again, but she was out of the office. Suspecting that it was likely another ovarian cyst (the first one had ruptured shortly after diagnosis), since she did not have a fever, could eat, and a quick abdominal exam (by me) didn’t reveal anything suspicious I waited until I could talk with the gynecologist. When we finally spoke, she sent us for an ultrasound, surprisingly, there was no ovarian cyst, nor could they find anything else abnormal. The gynecologist called us and wanted Emily to be seen in the ER or by the pediatrician. We saw the pediatrician, and it turned out what Emily was describing as abdominal pain, was hip pain! We did some blood work just to make sure that she did not have appendicitis and we were sent for an x-ray. The x-ray was negative but the bloodwork was abnormal. Her white count and her hemoglobin were low. The pediatrician wanted to do additional blood work to check for a vitamin B12 deficiency (a common cause of anemia), and check iron stores. Both were normal. I explained that Emily had always had anemia to a certain degree since infancy (but because of her “rough start” it was essentially ignored). Then he said something that got the wheel in my brain turning…” her anemia is probably because of her chromosome deletion”, and I think she should see a hematologist.
I recalled a story about a young boy in the UK who had a chromosome disorder and had something called Diamond Blackfan Anemia (DBA). This little boy was super sick, relying on blood transfusions, and in need of a bone marrow transplant. Emily was certainly not that sick. I spoke to my husband about it (he is an adult neurologist), and he told me to do the research. I spent hours on Google trying different combinations of words to find what I was looking for (3q29 and anemia, 3q29 and Diamond Blackfan Anemia; anemia and chromosome abnormality). There was plenty of information out there, most of which lead to DBA. I read all the journal articles that I could find on 3q29 syndrome, anemia, and DBA. I stumbled on the OMIM.org website. This website contains information on human genes and genetic phenotypes. In doing my research, I knew that there is a specific protein found on chromosome 3q in the 29 region (where her deletion is). I entered Diamond Blackfan Anemia into the search box on the OMIM website and saw that there is a gene on 3q29 (RPL35A) that codes for DBA. Now I knew from my research that she didn’t have a “typical” case of DBA, because there are certain facial and body features people with DBA have, and she does not have them, she also is not transfusion dependent as most people with DBA are. However, she met other criteria: anemia before the age of 1 (maybe it wasn’t her “rough start” after all), large red blood cells (macrocytic anemia), low reticulocyte count (new red blood cells). I was armed with all this knowledge before I even had the appointment with the hematologist. Over the course of three different hematology appointments we checked different reasons for the anemia. I continued to do my research and send it to the hematologist via e-mail. He read every article I sent, he listened to every concern that I had. He wasn’t sold that she had DBA but the “easy” blood testing that he was doing was coming back normal. He drew one final genetic test and decided that he needed to look at her bone marrow. We set the appointment up for May (2017). On the day of the bone marrow biopsy, the hematologist handed me the blood test results from the genetic testing he did. It showed that she is missing the RPL35A gene and because of that she has DBA, an “atypical” case (DBA 5 caused by a mutation of the RPL35A gene). What this means for her is that she needs frequent (every 6 months) blood counts (CBC) and a bone marrow biopsy every year. DBA is a bone marrow failure syndrome. The biggest fear is that she will develop myelodysplastic syndrome (MDS), a bone marrow cancer (essentially bone marrow failure), that will transition into leukemia. The worst-case scenario is that she will need a bone marrow transplant. Emily does not have any full siblings, she has half siblings, so that could pose a problem if she needs a transplant. Her second biopsy was done in May of this year and was negative.
My advice for anyone reading this article is to always go with your gut. You know your child best. Research, research, research until your eyes are blurred and your typing fingers are about to fall off. Find a doctor, nurse practitioner, or another medical professional that will listen. If they don’t listen either find someone else or scream loud enough that they must listen! Always err on the side of caution and for your child. Beware of scams and easy fixes. Unfortunately, there are people out there disguised as friends and medical professionals willing to see you almost anything for a “cure”. Do your due diligence, if it sounds too good to be true, it usually is! The last piece of advice I have is to love your child, unconditionally, for he/she is fearfully and wonderfully made! Perfectly imperfect.