Mayo Clinic Visit – Part 3

The end of our long week at the Mayo Clinic in Rochester Minnesota was coming to an end. There were still many conversations to have and specialists to meet. Kate was doing well. Her stamina was good, but she had a vomiting episode one night that had me worried we might start an episode while on our visit there. Thankfully that did not happen – though perhaps it may have led to more insight into her condition (?)
For a 2-year-old child, Kate handled the visit well. We still had to contend with entertaining her in waiting rooms, and ‘wrangle’ her during our meetings with specialists. Of course she had to be present – after all, this was all about her – but it would have been so much easier and less distracting to have her out of the room. In fact, in a few situations, my mom would leave the room with Kate and take her for a walk.

October 26th, 2009
We were having our second, and more in-depth meeting with medical metabolics, Dr.Gavrilova. She reviewed with us her impression of Kate’s history combined with test results such as recent bloodwork, and the muscle biopsy specimen from CHEO. She felt all symptoms pointed to mitochondrial disease.

As I have suggested before, being told you have mito is like being told you have cancer. There is incredible variability and severity in the disease. Some present as mild – and treatable/manageable, while other forms of the disease will undoubtedly result in death. Mito can strike many different organs and systems of the body – or multiple systems at the same time. It also strikes children and adults (i.e. it is not always a childhood disease).

For Kate, there was no specific amino acid abnormality that could be found – all were high. In the case of specific disease presentation for mito, if there are 2 or 3 high (for example), that helps to point to, or specify, a particular type of disease.

We discussed the testing that had been done by and/or coordinated by CHEO. Their testing had been extensive and has covered almost all the bases. Kate’s blood and muscle tissue had been sent to the McMaster University Health Sciences Centre, Baylor University in Texas, Columbia University, Boston etc.

Further, Dr.Gavrilova felt that if Kate had a form of mitochondrial disease she appeared to be on a milder form of the spectrum.
I found this an interesting comment/assumption this doctor how had not studied Kate extensively, nor had she done any of the primary testing or analysis of Kate. Further, she did not have a concrete diagnosis for Kate – so how could she make this assumption? I filed the comment in the “general comments” section of ongoing file in my mind re: Kate.

In discussing Kate, she described how her lactate were around 2.7, i.e. within normal range, but had been in the high range during her episodes. Elevated lactate is a typical symptom of mitochondrial disease. However, Kate’s muscle enzymes were fine, and there was no specific pattern to her symptoms that suggest a specific type of mito.

There are some well documented forms of mito that are described in the literature: MELAS, MERFF, MNGIE, Leigh’s syndrome etc. that have specific presentations of a cluster of symptoms and can be tested for via genetic/blood test.

Dr.Gavrilova also suggested that Kate undergo a second muscle biopsy and that a fresh sample of tissue should be analyzed – rather than frozen first as we the case in the first sample.

 

Dr.Mack – Neurology

This was our third visit to neurology at Mayo and our second with Dr.Kenneth Mack, who had appeared to have taken a keen interest in Kate. He was very well prepared with knowledge of her history and keen to help us sort out how to manage Kate more effectively in the absence of a diagnosis – though he did weigh in on that front as well.

I wanted to discuss pain management with Dr.Mack. Kate had a significant amount of pain with her episodes. Something I felt so deeply painful as a mom since her pain was not managed well. It is a caution to other parents with young, non-verbal, developmentally delayed children. They cry when they are in pain or distress, they have no other way of expressing it. And in my opinion, they are not ignored but they are also not assessed and treated as quickly as someone crying out with words. “Children cry” seems to be the understanding and to me – it appears it delays any intervention.

I feel like doctors are used to children crying and that this does not always call them to action. I felt so strongly about advocating for Kate’s pain management I did extensive reading on it for non-verbal children. I eventually sought out the pain management team at CHEO to assist me in assessing and treating Kate. What I found most distressing was working with teams of residents and doctors who did not know Kate who would take a very slow and  controlled approach to administering pain medication. I can recall one visit where Kate was clearly in pain, I asked the nurse to get me the resident. When the junior resident came in and I described what I felt I was seeing and my request for morphine for Kate (which what we were using at the time), she said she would need to consult the ‘senior’ (senior resident). She was gone for more than 20 minutes. Now let me pause her and ask you – would you wait 20 minutes for pain management to even be assessed let alone administered? No – neither would I. I did not let Kate wait either, I called the on-call pain management doctor who arrived at Kate’s bedside before the senior resident did. He prescribed morphine for Kate.
This is the difficult of pain management in young children. I am grateful that I know what to do and who to call, and I realize the assessment for Kate is made more difficult because her lack of case coordination at that time. But to watch you child cry out, to writhe around in her bed, to look at you with pleading eyes, and to eventually give up – it is absolutely heart wrenching and it should not happen.

So, I was keen to talk to Dr.Mack about what he would suggest. Tylenol and Advil combined sometimes worked for Kate. Other times we needed to move to morphine (which made me nervous) which worked well. Interestingly Dr.Mack suggested that morphine did not work well for migraine variant syndrome – which he felt was the underlying cause of Kate’s cyclical vomiting. He suggested instead a Tylenol suppository (if Kate was vomiting) combined with anti-nauseants such as Phernegen. He was also a strong advocate of IV hydration at the onset of symptoms. To this day IV hydration is the first and most important part of Kate’s protocol when she has an episode. 

Dr. Mack advocated again to re-try amytryptiline with Kate. He said that in 90% of cases of cyclical vomiting syndrome it works. He suggested we needed to try this drug longer (we had tried it before) and at a higher dose (which we would have to build up to). He counselled me to do further reading at the American Council on Headache Education.

I then asked the question that burns in my brain (do you know what is wrong with my daughter). If this wasn’t mitochondrial disease, what would it be?

Dr. Mack replied that the top 10 choices for Kate was that this was some form of mitochondrial disease – perhaps a phenotype of one of the known mito diseases – but that we may never have a confirmed diagnosis. He called Kate’s mito disease a ‘working diagnosis’.

(A “phenotype” is basically like saying it waddles, quacks, looks like, has webbed feet, a bill, feathers etc. etc. like a Duck..but we can’t confirm it is a duck).

 

Could it be this duck?

Could it be this duck?

Or is it this duck?

Or is it this duck?

 

Dr.Mack also broached the topic of the “mito cocktail” a very popular cocktail of supplements that supposedly helped to manage and/or alleviate the symptoms of mitochondrial disease. There had been much debate among Kate’s doctors about starting the cocktail and about its effectiveness. We had been counselled so far to not go ahead with it as there was still too much uncertainty about Kate’s disease and the benefits, but also the problems of starting on the mito cocktail. Further, the research and science was very limited with much of the evidence being anecdotal. Still, her was a Mayo clinic neurologist advocating that we may want to try it with Kate. It was certainly a conversation I would try to have with Kate’s CHEO doctors again.

Dr. Mack reviewed a few other questions we had such as:

– What about Kate’s chronic constipation?
A non issue for Dr. Mack and certainly not the cause of her episodes, though constipation would become worse with dehydration.

– Were vaccinations safe:
For the most part yes. But part of the pertussis vaccinations is typically withheld in mito-kids.

This was our last visit with Dr.Mack and at the end of it he handed his business card asking us to stay in touch and to feel free to follow-up with him if we had any further questions. Though to this day I haven’t been back in touch with Dr.Mack, I have a strong respect for him and think of him as part of Kate’s broader medical team.

 

Dr.Rodriguez – Hematology

We had met with Dr.Rodriguez at the beginning of our visit to Mayo, but as she did not have all the lab specimens and information about Kate, we had rescheduled our visit for later in the week.

Dr. Rodriguez reviewed with us what we already knew about Kate’s red blood cells (RBCs). She was producing them, but they were small (microcytic), pale (not red, but a pale pink), and misshapen. This would impact Kate’s ability to utilize/metabolize iron properly (i.e. she has iron, she just can’t use it). This is why a ‘sideroblast’ or ring of iron forms.

Dr.Rodriguez felt that there was really no intervention they could do other than watch and monitor. Kate’s Hbg did not drop below the low 70s and would rebound to the low 90s – neither level required transfusion (120 would be normal). She felt Kate’s sideroblastic anemia was a ‘anemia of chronic disease’.  She felt that if Kate’s episodes became less and less, her Hbg may normalize. She described this a function of Kate’s bone marrow, which is an organ of the body and mirrors how the body is feeling. Kate’s RBC could not normalize because of her illness.

Dr.Rodriguez did not have a suggestion of an underlying illness for Kate.
We now know that it is a key feature/condition of Kate’s rare form of mitochondrial disease.

 

And that concluded our visit to Mayo. Seven days of intense medical discussions about my daughter. Hoping for answers.

What I did come away with was a renewed confidence that our children’s hospital had been doing an excellent job for Kate – from a diagnostic point of view. Their suspicions of mitochondrial disease were confirmed and they were on the right path with testing.

What we did not come away with were clear answers or a new direction. And in the end, perhaps the visit was not necessary, but it give me the confidence that we were starting to exhaust all channels in hoping for a diagnosis for Kate. The visit to Mayo may not have been a ‘success’ when it came to answers, but in the bigger picture it was a necessary step.

 

Julie

 

 

 

Mayo Clinic – The Visit Part 2

The continued story of our visit to the Mayo Clinic.

October 23rd
We started our long day with a visit to metabolics. A detailed history was taken and we reviewed the family genetic history that I had provided a couple of days before. There was much discussion and review of Kate’s “episodes” and detailing what exactly occurs. We discussed specifics such as Kate’s blood lactate, muscle biopsy and results, and carnitine levels etc. I am still amazed at the amount of medical information and detail I carry around with me in my head. Details memorized and complicated medical jargon understood and able to be discussed as needed. (Where did I put that MD diploma?).
The metabolics resident – yes, we met with a resident first – was very interested in Kate’s sensory neural hearing loss, developmental delay, sideroblastic anemia and her episodes. She felt they are clearly pointed to a metabolic disorder. Again, this was not news to us, but good to hear from yet another source.
Something that was explained to us that I did not fully appreciate were the muscle biopsy results. Kate’s results were coming back negative for mitochondrial disease. In brief, she had many mitochondrion in the muscle and they are appeared to be healthy/normal. What was explained to us at the Mayo Clinic is that the tissue biopsy needs to come from affected muscle and/or the brain. A negative result can simply mean that tissue is not affected – at that time. As I have said before, mitochondrial disease can be a bitch to diagnose.

A Lesson on Mito
I got an extensive biology lesson at Mayo about mitochondrial disease:
– in kids the more common causes of mitochondrial disease are the nuclear genes (maternal DNA)
– mito is very difficult to diagnose (better now in 2013)
– not all mitochondrial diseases cause increase lactic acid in the blood or prolonged elevated blood lactate
– not all tissue are affected, e.g. in Kate her muscle tissue of the large rectis femoris leg muscle may not yet be affected, while other areas of her body are
– additional tests can be run on Kate’s tissue samples including; DNA deletion sequencing (I thought we had done that), expanded muscle tissue analysis (seems vague), and an EEG when she is having an episode.

We left this first meeting with metabolics feeling no more informed, but interested in what their attending physician would have to say once Kate’s muscle biopsy tissue arrived from Canada and was analyzed. Something that had not been sent in advance.

Our second meeting that day was with Dr.Mack from neurology.
Dr.Mack had reviewed the detailed information provided to his resident and had asked to meet with us again as our last meeting was cut short due to a long day for Kate.
Dr.Mack was convinced that Kate’s ‘episodes’ were episodes of cyclical vomiting syndrome. He felt that a drug cocktail would be able to slow/stop the episodes or at the least reduce their intensity. He proposed Amitryptiline and Riboflavin. He expected episodes to reduce in frequency and intensity and if not – then an extensive GI workup should be done.
Dr.Mack described to us how cyclical vomiting can be common as a stand alone condition at this stage/age in children, and it could be they way mitochondrial disease was presenting. He further described how it could be severe enough to last several days and require hospitalization as had been our experience to date. Though Kate had been prescribed amytriptyline before – Dr.Mack felt the dosage needed to be much higher which would require ‘ramping’ up the dosage over time and watching carefully for side effects such as; increased appetite, listlessness, prolonged QT on EKG.
I was skeptical about amytriptyline. Though cyclical vomiting syndrome seemed to fit for Kate, we had tried amytriptyline before and found Kate had side effects that were disconcerting for us; loss of balance, frequent falls, listlessness. I was not keen to try the drug again – but since it was being recommended by another neurologist (from Mayo), I felt like we should.

We also discussed with Dr.Mack Kate’s global developmental delay and her progression. There had been little information about Kate’s brain myelination pattern since her first MRI at the age of 12 months. A subsequent MRI showed little to no change and the information itself was not a diagnosis or a condition, it was simply a fact that Kate’s white matter was developing slowly and perhaps not creating the neural synapses her brain required to carry information from one area to another. Further, there can be no prediction on development with only this information, and there was nothing more we could find to describe Kate’s developmental delay. Dr.Mack was clear with us that Kate’s delayed myelination pattern was not causing her developmental delay, but that it was part of the bigger picture of Kate’s condition. As for a prediction for development we should look at the near past (3-6 months) as a prediction for how her development will progress. The long-term can’t be predicted with any accuracy.

And then we heard the words again, Mito is very difficult to diagnose, though with Kate’s clinical picture it is the top of the list.

You know what that makes me think of everytime I heard it…this…

What to expect when you expect mitochondrial disease.

What to expect when you expect mitochondrial disease.

 

Later that afternoon we were to meet with Dr.Lloyd, the coordinating pediatrician at the Mayo Clinic to have a ‘touching base’ meeting to discuss how our visit was going and any concerns we might have. I made a list to discuss at the meeting:

1. What is an appropriate protocol for Kate when she has an episode? i.e. at the ED
2. What other medical conditions can we expect Kate to develop?
3. Vaccines – are they safe for Kate? Should she follow the regular schedule
4. Can we review the step metabolics (at Mayo) are taking to diagnose Kate, e.g. deletion profile, mito DNA and nuclear DNA etc.
5. What is the working diagnosis for Kate?
6. Where can we find reliable, scientific information on mitochondrial disease (diagnosis, treatment, description)
7. What is the difference between a metabolic disorder and mitochondrial disease?
8. Discuss the proposed GI tests and the importance of doing them (i.e. neurology thought we should wait and go step by step)
9. Bloodwork results, bone marrow biopsy slides, muscle biopsy slides (have they arrived from Ottawa)?
10. What is the risk that Kate might suffer a catastrophic event due to this disease. Is there a spectrum?

 

 

Julie

Kate’s Story

One of my favorite pictures of Brian and Kate. Not yet walking, very tiny – and dancing with her dad.

The spring of 2009 was extremely difficult for Kate. She was chronically unwell and suffered a major episode of what we now know was Cyclical Vomiting Plus Syndrome. Along with that episode, Kate suffered other complications that resulted in her being admitted to the pediatric intensive care unit at CHEO. Even after discharge, Kate continued to suffer from fatigue, lethargy, irritability, chronic constipation and feeding difficulties. We had some hope for progress; there were many diseases being investigated as possible underlying causes for Kate’s increasing list of medical conditions, and the medical team had met to discuss the need for a second opinion in several areas as well as better case coordination for Kate. We had been struggling to find help for Kate, and had felt very frustrated with the journey so far – so the hope for case coordination really lifted our spirits. At the same time, we had begun looking into our own second opinion possibilities at the renowned Mayo Clinic in the US, which seemed to be the best option of the several we investigated, to take a comprehensive look at Kate’s case.

June 2009

Metabolics:  Kate had been treated for several months now with a thiamine supplement in hopes that her blood disorder might be a form of Thiamine Resistant Myeloblastic Anemia, however after several months of treatment there was no change to Kate’s hemoglobin level or mean cell volume (a measure of the average red blood cell size). Further, genetic mapping for TRMA showed no abnormalities. Kate stayed on thiamine supplementation for a few more weeks, but in the end this treatment for her anemia was abandoned.

Gastroenterology:  Kate had a small bowel follow through procedure in May to examine how her bowel was functioning and look for any structural abnormalities. This is a nasty procedure that required Kate to drink ‘barium contrast’. I tried to deliver it to Kate in her bottle, but after the first few sips she quickly realized this was not her regular formula. (If you’ve ever tasted barium you’ll know it has a nasty chalky taste). The nurse came by to see how much Kate had ingested and told me she had to drink at least an entire 12 ounce bottle. I wasn’t sure how this was going to happen, and felt pretty frustrated that this was the only way to get contrast into Kate. I mean, we were at a pediatric hospital you would think there would a better process?  Eventually after much struggle with the bottle and barium contrast being spit up on me and the floor, I asked the nurse for a large syringe so that I could syringe the contrast into Kate. This took another 20-30 minutes and more struggling and crying, but eventually the contrast solution was dispensed to her little gut so we could proceed to the x-ray.

X-ray for small bowel follow through (SBFT) is a 2-3 step process. You capture the first image right away as the barium starts its decent through the bowel and then you repeat the image 20 and 40 minutes later to see how it has proceeded along its winding route, noting blockages, obstructions, or structural oddities. Kate’s SBFT showed constipation and a secum that was not fully descended. Neither was a huge concern, but indicative of Kate’s persistent and systemic hypotonia lending itself to a sluggish digestive system. There was some concern about whether or not Kate might be having some sort of bowel rotation during her episodes – which would explain her pain. This could only be investigated during an actual episode by x-ray, so we would have to wait until Kate was unwell again and have gastroenterology paged.

Kate continued to be treated for her reflux (GERD) and was prescribed polyethylene glycol – better known as PEG 3350. PEG is a osmotic-type laxative that works by holding water in the stool to soften it and increase the number of bowel movements. Kate continues to take PEG almost daily.

Sick Kids Hospital:  In June 2009 we had our first consultation with a specialist at Toronto Sick Kids Hospital for a second opinion on a diagnosis for Kate. We met with a specialist from neuro-metabolics, Dr.Teine. As we drove to Toronto, Brian and I made a list of our goals for the meeting.  First and foremost we wanted a diagnosis for Kate. If that wasn’t possible we wanted to better understand how to keep Kate safe and feeling well. Was there a treatment for Kate? We were no longer comfortable with the watching and waiting approach to her care and wanted more decisive action.

Dr.Teine talked about mitochondrial disease and Kate’s bowel issues. She felt this was the strongest clue to what might be going on with Kate. She suggested we video Kate’s future episodes for her specialists to give them a better understanding of what was happening at home. She also wanted Kate tested for Rett Syndrome and MNGIE (which is a form of mitochondrial disease). When she explained to us what these two conditions were about, we could not believe this might be what was happening to Kate. However, at the same time as feeling upset and anxious, we felt hopeful that there might be another area of investigation we had yet to explore,.

This is the true emotion of parents caught up in diagnostic limbo – sometimes the horrible and awful diagnosis can be better than the not knowing.

July 2009

Orthopedics: Kate has been referred to orthopedics by neurology. Kate is still not walking at the age of 20 months and there is some concern as to whether or not she has a curvature in her spine. Upon examination, Kate is felt to have only a mild curvature and that it should not be impeding her ability to walk.

General Pediatrics: After the May 2009 medical team conference about Kate, it was decided by all of the specialists in the room (about 10 at that point) that Kate’s case clearly required coordination within the hospital. We felt very happy about this assessment as we had been struggling to be Kate’s ‘case coordinators’ and medical advocates for close to a year, a role that is very difficult for parents to maintain. Unfortunately, despite the best intentions of this team of medical specialists CHEO had no program in place or infrastructure set up to facilitate case coordination for a medically complex child being followed by several different specialists within the hospital. Eventually it was decided that Kate would be referred to general pediatrics, with the idea that a pediatrician from this clinic could perform the function of case coordination. Despite 3 different referrals to general peds at CHEO, and follow-up phone calls from Dr.S, discharge planning and social work, we never once heard from them.

Mayo Clinic: In collaboration with our consultant pediatrician, Dr.S, Brian and I had started the ball rolling for a visit to the Mayo Clinic pediatric facility in Rochester Minnesota. Preparing the referral package that was to be sent to Mayo fell to me, and it was a very detailed and process. Mayo required extensive documentation about Kate: doctors notes from GI, neurology, metabolics, genetics, hematology, endocrinology, neurosurgery, audiology, orthopedics; diagnostic imaging, including all of Kate’s MRI, MRA, MRS and CT scans; detailed bloodwork results from the last 12 months; muscle biopsy and skin tissue sampling; bone marrow biopsy sampling; and, hospital admission and discharge notes. I spent weeks pulling together the information, and included my own summary information and charting that I had begun to develop for Kate’s case. In the end, we pulled together 3 packages – one to be sent to Mayo, one for Dr.S, and one for my own records.

What we had not examined with respect to Mayo was ensuring whether or not OHIP (our provincial health insurance plan) would facilitate covering the costs for Mayo. In the end we had to delay our August meetings into October so that the insurance coverage could be sorted out.

In the meantime, CHEO had new lines of investigation for Kate’s underlying diagnosis that included: celiac disease (to explain her GI symptoms), myasthenia gravis, autoimmune disease, as well as following up on the diagnostic testing for MNGIE and Rett Syndrome as suggested by the neuro-metabolics consult at Sick Kids.  There was also concern about Kate’s lack of weight gain since January 2009. We completed the out of country diagnostic forms required to undertake the testing and sat back to wait again hoping for some word about a diagnosis for Kate.

August 2009

Sick Kids Toronto: In August 2009 we met Dr.Yigal Dror at Sick Kids for a second opinion from hematology about Kate’s unusual microcytic anemia which was highly suspected to be sideroblastic anemia. Dr. Dror reviewed Kate’s history with us – again we told the story of the pas 20 months in as much detail as we could. Dr. Dror thought Kate’s bone marrow biopsy (BMB) should be repeated to see if there are any changes in the red blood cells. If she did not have sideroblasts on her next BMB, then this would lead to other areas of investigation.  He also had suggestions for additional diseases that may be causing her conditions. He was highly suspicious of Pearson Syndrome – an area of investigation already underway, and he also thought that Wolfram Syndrome was highly suspicious.  Sideroblastic Anemia with Ataxia was also discussed and Dr.Dror suggested testing of the PUS1 gene if possible and suggested that Kate’s blood be sent to a facility specializing in sideroblastic anemia in Bishop, New York.

Dr.Dror was impressed with how provocative Kate’s underlying symptoms were and considered it very unlikely that they were unrelated. He also noted that it was important to fully investigate Kate and identify all of her underlying conditions so that she could be treated appropriately

In August 2009, we met with Kate’s neurologist Dr.D to review the specialists opinions from Sick Kids. What had become apparent was that we were no further ahead with answers, and that more diagnostic tests were being suggested to further investigate Kate.  Repeat MRI, bloodwork, and muscle biopsy had all been recommended by Toronto. However, there were many outstanding tests whose results could have some bearing of what was going on, so we were not in a rush to put Kate through more invasive tests. We felt somewhat deflated from our hope that Sick Kids would have answers for us, and we felt frustrated by the continued gap in coordinated care for Kate within CHEO. We shifted our focus to our next plan.  As her parents we were now putting a lot of hope in the renowned Mayo Clinic doctors and hoping that they would be able to help Kate. They examined and treated very sick children, and highly unusual cases all the time and we truly felt that they could help us find the answers we needed.

Julie

Kate’s Story – Intensive Care April 2009

When Kate was 18 months old she suffered a serious episode of Cyclical Vomiting Plus Syndrome. We did not know what it was called at the time, we called these episodes of frequent acute illness her ‘episodes’. We had been seeking help for Kate for months. We were looking for guidance and leadership for her diagnostically and with care for her multiple medical conditions. We had excellent specialists involved, but without a unifying diagnosis, no one seemed prepared to take the lead on Kate’s case.

April 23rd, 2009

Kate and I arrived to the emergency department at 5:30 p.m. It was early evening, and there was an line up literally out the doors of the emergency department. Kids with their parents looking feverish, snotty, coughing, crying and generally unhappy. As I stood in line with Kate, she had become very quiet. She dozed against my shoulder and didn’t seem to have the energy to lift her head. The fight had gone out of her. For a moment I thought to myself, “maybe I’m wrong about this – maybe she’s fine and really not that bad – this is a long line up, perhaps we should just go home”. As we arrived at the triage desk, a young mom rushed by yelling for a nurse. Her daughter had cut her finger on a sharp can. There was a bloody bandage on the finger and a flap of skin that looked pretty gross. But the bleeding had stopped and the nurse calmly guided the mother to a seat and told her the finger looked ok and that she would need to wait her turn for triage. Kate and I approached the desk, handed over our health card, and in my fatigued state I tried to briefly relay what had been going on for the past several days/weeks. It was/is almost impossible to relate what is ‘wrong’ with Kate in a short conversation. I should have asked, “Do you have 20 minutes”?

When I mentioned that Kate was being followed by metabolics at CHEO that seemed to get things moving a little more quickly. Kate was taken back for a triage assessment at which point everything moved at an accelerated pace. Kate had high blood pressure,her oxygen saturation levels were in the mid 70s, and she was tachycardic (very high heart rate). She was marked as ’emergent’ on her chart and Kate was taken to a ‘resus room’ which is an area of the emergency department where children are taken for immediate treatment. We were soon surrounded by doctors and nurses who were assessing and treating Kate. Bloodwork was immediately taken and the team worked to get an IV into Kate so that they could provide IV bolus, which is a large volume of fluid given over a short period of time. Kate was acidotic – indicative of severe dehydration.

The metabolics team was called, and the resident ordered a full metabolic work up on kate. The ICU (Intensive Care Unit) was also called for a consult and ordered a portable chest x-ray for Kate as they were considering pneumonia and started immediately treating her with an antibiotic. Zofran was also ordered to combat the nausea and dry heaving. The emergency team also considered administering chloral hydrate – the sedative that had been prescribed for Kate which we had not yet used. The idea was breaking the ‘cycle’ of pain and irritability she was in. Neurology was consulted, and felt this was ok, but as her parents we objected and expressed our concern that with low O2 saturation and the pH levels she had, we were not comfortable sedating her.

By 11:30 p.m. that evening, Kate had received 5 IV bolus of fluid. She was still in emergency resus and was being transferred to the PICU (Pediatric Intensive Care Unit). Dr.C had been paged and was coming to see Kate in the morning.

At 2 a.m. Kate and I arrived at the PICU. Kate was now on oxygen to help facilitate her O2 saturation. She was acutely acidodic with a very high anion discrepancy. She received further IV bolus and now had potassium added to the fluid in order to balance her electrolytes.

At 3 a.m. the team required further bloodwork to assess Kate’s condition. Kate’s body was in a such a state of dehydration and shock that the nurses were unable to locate a vein to get blood. Kate was poked in the arms, wrists, hands, feet, and head multiple times. Despite her severe state, Kate cried – producing no tears. Then she slowly began to give up and not fight any longer. I held her each time she was poked and tried to reassure her, knowing that this was all so awful, but necessary.  The anesthesiology resident was called to try and access a vein – with no success – and at this point I had asked to excuse myself to a chair. I couldn’t restrain Kate any longer. The toll on me emotionally was too much. The VAT (veinous access team) were called – with no success. Finally, after about 2 hours of attempts to draw blood the team decided to try an arterial blood draw which was performed by the anesthesiology resident. Blood was finally taken.

Over the course of that night, I lay in bed with Kate stroking her head. She was sleepy, but fitful and clearly exhausted. It seemed I could not comfort her, and I felt at a loss of what to do.

The next morning was a flurry of activity with consultations with Dr.C (metabolics); Dr.D (neurology); Dr.G (nephrology); and, Dr.S (endocrinology) – all specialists that continue to follow Kate to this day as part of the medical team at CHEO. More blood was taken and urine samples were analyzed. Kate was scheduled for a CT and MRI Spectroscopy. (MRI Spectroscopy measures biochemical changes in the brain. While MRI identifies anatomical abnormalities, MR spectroscopy compares the chemical composition of normal brain tissue with abnormal tumor tissue). I called Dr.S and he came to see Kate that afternoon to discuss the situation – but mostly to support me, for which I am ever grateful. The focus for that day was stabilizing the severe acidosis due to dehydration. My focus was on trying to make Kate more comfortable and to have the team help her with her pain.

April 25th

Kate had a difficult night of restless ‘sleeping’. She moaned during the night as was clearly uncomfortable. She seemed less responsive than the previous day. She put up no fight with the nurses or bloodwork. What was most unsettling to me is that she would look at me, but not seem to really see me. Her oxygen saturation levels were still very low and the team was conferring on what to do next. It was decided that they would do another chest xray, and that a lumbar puncture might be appropriate to check for meningitis. Nephrology were considering many renal failure scenarios based on Kate’s urinalysis and metabolic concerns. Kate’s labs were indicative of a condition called renal tubular acidosis, which is not a diagnosis but a symptom of a further condition. In Kate’s case it was finally determined to be transient (occuring in isolation and not chronic). Kate’s unrine had protein in it and hypercalciurea (a significant loss of calcium), a condition she continues to be treated for to this day.  The team felt this might help explain the acidosis, but it was not telling the full story, so an immediate ultrasound of Kate’s kidneys was ordered.

That evening, Kate’s CT results came back and appeared normal. A LP (lumbar puncture) was ordered for that evening – those results were also normal. Kate was starting to be a bit more awake. She was opening her eyes and watching me. She was begining to sip from a bottle. As long as she was given medication for discomfort, she seemed to settle and be able to sleep. I made a list of what was being considered:

– elevated aldosterone levels

– Sistenosis (lab samples sent for testing)

– Pearson Syndrome (now ruled to be ‘not likely’)

– Thiamine Resistant Megaloblastic Anemia (awaiting test results)

– Mitochondrial DNA deletion sequencing (now ruled ‘not likely’)

– lactate levels

– echocardiogram to examine enlarged heart that was identified via chest xray in PICU

– sideroblastic anemia

– developmental delay

– delayed myelnation on MRI

– lethargy and irritability (ongoing)

– acidocity

I also added to my list that our biggest question and issue for discussion was how to manage further episodes – a plan, and to have a letter for emergency to give to triage.

April 27th

Kate recovering from and episode of cyclical vomiting plus syndrome and severe dehydration. April 2009.

Kate had stabilized enough to move her from PICU to the floor on 4 East. I was nervous about the move. You get into a sort of state with the constant care and fishbowl existance of PICU that you become a bit dependant on the level of care. Kate was still not well, but she was stable and she became a little more of our responsibility to care for.

She remained on oxygen and IV fluids. I was beyond exhausted, but unwilling to leave Kate. Brian and I finally decided on a ‘day’ shift/ ‘night’ shift role that we continue to this day. I would do the day when there was the most action with specialists, and Brian would stay the night with Kate. We entered a routine of coaxing fluids and food into her, weighing diapers, administering medication, facilitating exams by nurses and the medical team. Kate was slowly recovering and there was nothing to be done but to support her as she slowly came out of her episode. Exams and tests were ordered and my mom arrived to lend support as well. An MRA was added to the list of tests as was testing for biotinase deficiency and a skin biopsy. (MRA, magnetic resonance angiography is used to generate images of the arteries in order to evaluate them abnormal narrowing, occlusion or narrowing and risk for rupture.)

The team had been conferring about Kate’s case during this admission and were clearly in agreement with us that something needed to be done to better facilitate the coordination of her care. A social worker from neurology was assigned to Kate’s case, and Kate was referred to the palliative care program.

A note about pediatric palliative care:

When people hear that Kate is a palliative care patient, they often looked shocked and concerned. It’s important to know that pediatric palliative care is different from that of the adult population. Palliative care in the peds population does involve ‘end of life’ care, but it is much more thant that. Palliative care patients in the pediatric population are children who have life limiting disease, and who require pain management and respite support. Kate qualified for both of these.

Kate’s medical team also organized the much awaited and requested medical meeting to discuss her case. As her parents, we asked for 3 specific items to be discussed:

1) That we be referred for a second opinion concerning Kate’s case, and that the following be discussed:

– where would we go for this second opinion – when will this happen – what specialties will we meet with

2) That we wanted a crisis letter for medical triage at CHEO emergency department which would include: an intervention/treatment guide for Kate’s episodes.

3) We asked for a discussion about better managing Kate’s discomfort/irritability/pain during her episodes.

April 30th

Kate continues to have discomfort and difficulty sleeping. Her IV is moved from her foot to her hand as the 1st site has become swollen and red. Kate successfully manages a general anesthetic administered so that the team can image for a MRI, MRS and MRA.

The team conference is held and we are invited to come in at the end of the meeting to hear what the team has decided for Kate.

Kate will be referred to Sick Kids in Toronto to examine bone marrow failure and her bloodwork will be examined by a lab in Boston specifically for sideroblastic anemia.

Kate will also be seen at Sick Kids by neurology and metabolics by a colleague of Dr.C.

Dr.B, Kate’s gastroenterologist has outlined further tests for Kate to explore the GI issues she is having, i.e. cyclical vomiting.

The referral letters will take 1-3 months and we will be supported by CHEO social work in making any arrangements.

Dr.Sp is now Kate’s palliative care doctor. He gives us a tour of Rogers House and discusses his role in pain management and palliative care support for Kate.

CHEO has also committed that Kate will have better coordination within hospital upon discharge, and that her discharge summary from this hospitalization will included a triage letter for the emergency department.

On May 4th, Kate is discharged from CHEO. She has not returned to her ‘baseline’ and is still unwell, but she is stable and has been continuing to improve. We discuss sleeping issues, discomfort, and fluid intake with the discharge planning nurse and clarify the procedures for the next episode Kate might (will) have.

We took Kate home after 2 weeks in hospital, but it was not to last long.

Kate’s Story

I have had a hard time getting started on writing this post. It’s been difficult because the next few months of Kate’s story were very difficult for us and culminated into an acute life threatening event for Kate that probably could have been prevented. If I knew then what I know now, we could have prevented what happened on April 23rd – but I didn’t, and reflecting back on the events of April and May 2009 is still very difficult for me.

March 2009

We were still waiting for test results from the February muscle biopsy. I guess back then, I was less informed about how long it actually takes to perform the complicated tests and analysis required when screening for obscure metabolic conditions. I spent a lot of time in between February and April 2009 speaking with the metabolics team – particularly the resident to Dr.C – and pushing for information. I know now that I was pushing for answers – but I was also looking for medical support, leadership and coordination of Kate’s case. We felt adrift when it came to Kate’s care and we had a sense of foreboding that something serious was going to happen and we would be ill equippped to manage the situation. It seemed to me at that time that metabolics was the obvious ‘lead’ for Kate’s case as they were taking on most of the investigation.

The metabolic team were looking at: respiratory chain enzymes and disorders of mitochondrial energy production with the idea that affected enzymes would then point to what genes might be affected and could be further investigated. Of note: the team had also ruled out Schwamman Diamond Syndrome. We made a list of issues we were following and ongoing questions we had for metabolics. We wanted to better understand Kate’s sideroblastic anemia, the increased alanine that kept recurring in her blood tests, and what interventions we could consider to keep her well.

On March 19th, I called the resident for metabolics again to tell her Kate seemed ‘off’. That she had been demonstrating the same symptoms we had seen before when she was starting an ‘episode’. It was made clear to us at that time, that they were not interested in Kate’s symptoms or how she was feeling since they were not Kate’s pediatrician or primary care team, and were not who we should consult when Kate was having an episode.  I felt frustrated and alone.

By April 1st Kate was still unwell. We had been rocking her and trying to keep her calm day and night.. She had no specific symptoms other than constantly crying, lethargic, and refusing to eat or drink. I took her to see Dr.S our pediatrician who noted nothing obvious after examining Kate, i.e. no focus or infectious process that would be making her unwell. I took the opportunity to discuss the stress we were feeling over Kate’s situation and the lack of leadership on her case. We felt that no one seemed to be ‘in charge’ within CHEO and among the various specialists, and we were not sure who we were supposed to consult about Kate and when. We thought a meeting of the specialists involved in Kate’s case would be important. We wanted to have everyone on the same page and have a focused effort on what all the different specialists were doing to help Kate. What we were asking for – but just didn’t realize it at the time – was case coordination for Kate. Dr.S understood the stress we were feeling and thought a phone call to ‘patient relations’ at CHEO might be a good idea. Patient relations help families to navigate difficult situations within the hospital – and they might be able to provide some assistance in facilitating better coordination of Kate’s case. In the meantime, Dr.S spoke with Dr.C and they both agreed that a ‘case conference’ to discuss Kate’s case would be an important next step.

April 6th, we met with Kate’s neurologist, Dr.D. We discussed findings in Kate’s bloodwork that he felt were important including low levels of carnitine and possibly supplementing her with co-enzyme Q10. We also reviewed the medication that Kate was on that was hoped to help her episodes, cyproheptadine, and the suggestion to start on a carnitine supplement. Dr. D had also ordered an EEG for the following day to check for seizure activity in Kate. We had reported that Kate had been ‘shaking’ and ‘rolling her eyes’ during the most recent episode. Kate did well during the procedure and to this day, we are not aware of any neurological seizures. She continues to have significant shaking during episodes which is now suspected to be a reaction to acute hypoglycemia.

April 20th, we finally had a sit down meeting with Dr.C from metabolics to discuss the muscle biopsy results, bloodwork findings and next steps in the investigation into the underlying condition affecting Kate. Having a conversation with Dr.C is like taking a crash course in micro-biology, bio-chemistry, physiology, and genetics all at the same time. Dr.C talked about enzyme respiratory tests, oxidative phosphorylation tests, mitochondrial DNA deletion, and increased alanine levels. Dr.C also wanted to discuss 2 new diagnostic theories concerning Kate: Pearson Syndrome as a metabolic condition and Thiamine Resistant Myeloblastic Anemia (TRMA) of which microcytic anemia and hearing loss are symptoms.  TRMA is also associated with diabetes so more bloodwork would need to be done to verify Kate’s blood glucose levels. Dr.C wanted to start Kate on thiamine right away and would repeat bloodwork in 4 weeks to see if Kate’s microcytic (sideroblastic) anemia responded to the treatment.

Dr.C also broached the subject with us of referring Kate to a colleague for a second opinion. This was the first time a second opinion had been mentioned to us.

Dr.C addressed the issue of a ‘diagnostic lead’ for Kate. While he did not volunteer for this role, he did tell us that he is often the doctor who deals with more ‘obscure’ cases because that is the reality of the metabolics/genetics world of medicine. He did not give us a clear opinion or direction on how to handle Kate’s episodes, but made clear he was not the lead for her case.

We still did not have a lead for Kate and we were feeling scared and frustrated. We knew Kate was unwell. Her quality of life was being significantly affected by her medical conditions and frequent episodes. Her development was falling behind, and we were exhausted caring for her.  We didn’t know how to help her and we felt she was unsafe. We didn’t know what to do – and we felt like we weren’t getting help.

April 22nd we contacted Dr.S again as Kate was unwell and vomiting. We asked again for a ‘team meeting’ that had still not been scheduled and our interest in the second opinion that Dr.C suggested. We began to take matters into our own hands as desperate and scared parents and we contacted Sick Kids about how to see a metabolic specialist, we also visited the renowned Mayo Clinic website about the process for being referrred there and discussed a referral from DrS. I started to build a comprehensive file on Kate and used my starting point with a summary document a medical resident had developed on her own from Kate’s voluminous chart. I also place a phone call to the patient and family representative at CHEO asking for help with Kate within CHEO.

April 23rd, Kate is still very unwell. I am concerned as she had been vomiting for the previous 24 hours, but had stopped vomiting overnight continuing to ‘dry heave’ between bouts of intense crying. I had not slept all night, and neither had Kate.  We waited until morning and then contacted Dr.S about seeing Kate again. Kate was lethargic, pale, listless and she had stopped crying. She was still wetting diapers, which we were using as our indicator for adequate hydration – we didn’t know at the time that Kate was having renal failure and could not concentrate her urine. The fact that her eyes were sunken, lips dry and and chapped, and Kate was not making tears had failed to get our attention. The signs of severe dehydration were sublte to us then. We discussed with Dr.S using the Rx for chloral hydrate to sedate Kate to help her get some sleep, but when we arrived home I decided against it. Kate looked so extremely unwell I was scared for her to go to sleep, we knew we needed to take her to the emergency department at CHEO.  We packed our bags and went at 5 p.m. that day.

Julie

This is Kate the morning of April 23rd, the day we rushed her to CHEO for the 5th time.