Kate’s Story – Procedures

January and February 2009 were very busy months with Kate. I continued to take Kate to her regular occupational therapy and physiotherapy sessions, and we had also begun auditory verbal therapy as we began to use her little pink hearing aids to accommodate her hearing loss and her delays in speech development. We had also come through a significant amount of tests including bloodwork, feeding studies and upper GI exams – and were awaiting results. Feeding continued to be a major issue for Kate. She had great difficulty chewing food and swallowing, and we had been working with an occupational therapist who specialized in feeding issues since Kate was 10 months old. We had not made a huge amount of progress and Kate was very small, chronically constipated and suffering from a reflux condition called GERD for which she was being medicated.

The ‘feeding occupational therapist’ had been slowly introducing water and homo milk to Kate’s diet. Water was going well, milk – not so much. We had come to rely on infant formula when Kate was not breastfeeding and that stayed the norm until Kate was just shy of 5 (yes, just recently). Kate was slowly progressing from infant foods into very overcooked vegetables. Texture and chewing seemed to be issues, so veggies my grandmother would have liked were Kate’s preference. We were also encouraged to give Kate lots of opportunity to touch and play with her food, and to take our time feeding her. I laugh a little now as I look back at my notes, feeding journals, graphs and charts about intake. We were ‘second time’ parents and none of this was new or unique information to us, yet it was made to seem like rocket science. As I look back the common denominator was not what or how we were feeding Kate – it was that Kate simply couldn’t or wouldn’t eat. It was difficult for her and it was uncomfortable, and whether or not that changed was really up to Kate’s body and not OT intervention. (Of course none of us knew that at the time.)

February 3, 2008

We had a consultation with the surgeon who would be performing the muscle biopsy on Kate’s leg. It was a General Surgery consult in Clinic C6 at CHEO. It would be the second time Kate would have an anesthetic. It would be first time she was operated on.

Kate woke feeling unwell that morning. She started vomiting and would not eat or drink. She was lethargic and moaning and clearly uncomfortable. She cried constantly, and especially when she was not held. Kate was having another episode and her surgery date was delayed.

In the meantime, CHEO genetics were still working behind the scenes and collaborating with 3 different medical facilities on Kate’s case. McMaster Health Sciences Centre, The Hospital for Sick Children (Sick Kids) in Toronto, and Texas Baylor University were now involved in various analysis of Kate’s bloodwork.

Sick Kids had completed genetic testing on Kate’s hearing and had concluded that Kate’s hearing was not genetic in nature. (Of course not all genes for genetic hearing loss are yet mapped).

Sick Kids had also come back with a suggested diagnosis of Schwamman Diamond Syndrome based on the symptoms that Kate was presenting with. Sick Kids was seeking parental consent to investigate Kate’s DNA for this disease.  The symptoms for Schwamman Diamond Syndrome are: short stature, anemia, pancreatic insufficiency, slow bone growth and fragility.

What was important to us was that something was being investigated and considered. Even when the diagnosis is not one you would ever want for your child, the not knowing seemed to somehow be worse. We hoped that Sick Kids had stumbled upon something, even as we were moving forward to pursue something else entirely.

February 20th, 2008 Kate underwent a ‘procedure surgery’ at CHEO toward an underlying diagnosis for her medical conditions. Dr.B, her surgeon performed a muscle biopsy on her left leg, extracting muscle tissue from her rectus femoris muscle, the largest muscle in the body and one which would be able to regenerate the muscle while still allowing mobility for Kate. The biopsy sample would be used to exam the mitochondrion at the cellular level for mitochondrial disease. That little sample would eventually end up travelling the world, and be seen and examined by renowned medical centres and metabolic specialists – and it would not provide a diagnosis for Kate.

The second procedure Kate underwent was a lumbar puncture to test for lactate in Kate’s cerebral spinal fluid (CSF). In the past, Kate’s bloodwork had shown elevated levels of lactate. The metabolic team wanted to confirm these results and gain further information as blood lactate levels can be variable and affected by many other factors. CSF lactate levels would give the team more information about respiratory chain disorders, infection/inflammation, other metabolic disorders – including possible mitochondrial disease.

Finally, a bone marrow biopsy would be performed on Kate. Her left iliac crest (the top back of her hip bone) would be punctured by a large biopsy needle right to the core of her bone marrow. This test was being done to further examine the nature of Kate’s sideroblastic anemia, which so far no one could figure out the cause and was determined as of ‘unknown origin’.  If you read the link on sideroblastic anemia, you will understand it is not a good blood disease to have. Kate’s condition was stable and still is, and I will describe more later in this post.

As with anything Kate related, the procedure surgery didn’t go as smoothly as we had hoped. Paperwork was mixed up and surgery schedules not properly conveyed and as a result there was no hematologist there to perform the bone marrow biopsy. I was with Kate this entire time and insistent they sort it out before I handed her over to be ‘put under’. There was no way we were doing this again with a third anesthetic procedure, and I was waiting for them to have sorted out the situation before they touched Kate. When hematology did send someone down to the surgical suite, I was pretty happy to see Dr.J, the hematologist we had been working with us thus far. She was there to personally perform the procedure. (She was the doctor who was amazed at Kate’s bloodwork during her first admission 4 months earlier).  I was finally ready to hand Kate over and was with her as they put the mask on her to help her fall asleep before they took her in for IV anesthetic and the procedures. I knew Kate would be safe, and it was the second time I had done this with her, but those eyes and the pleading look of “don’t leave me mommy” will always stay with me. As a parent all you can do is look calm and reassuring, while your heart breaks and your eyes well up with tears. The amount of trust a child has for their parent can rock your world.

When my little pin cushion woke for anesthetic she was clearly sore and uncomfortable. I was surprised at the size of the incision on her little 16 month old leg, but reminded myself we had done this for something very important.

Muscle Biopsy February 2009

Bone marrow biopsy February 2009

Our little pin cushion – Day 4

February 27th, 2008 we met with a new hematologist to discuss Kate’s hematological and bone marrow results. Dr.K had now taken the lead on Kate’s case, and he remains our hematologist to this day.

Dr.K reviewed with us that over the past 6 months Kate’s hemoglobin has been consistent at 80-90 g/L (normal for children would be 115-160 g/L). Dr.K told us that this level of hemoglobin can be tolerated and is adequate for O2 (oxygen) transportation to the cells of the body. In short, Kate’s hemoglobin was quite low, but it was stable and that was good.

Normal red blood cells

Dr.K told us Kate had very small red blood cells, which were abnormally shaped and of abnormal color. Red blood cells should be round, red, and concave at the middle with a fat outer ring. Kate’s were misshapen (oval), very small, pinkish in color, and convex at the middle. Kate’s bone marrow biopsy results showed that she had enough cells to produce hemoglobin, but that ‘sideroblasts’ were also present in her red blood cells, demonstrating that though her body had adequate iron there was an inability to use it to produce hemoglobin. Dr.K told us this points suspiciously toward mitochondrial disease.

What does hemoglobin do?

Hemoglobin in the blood carries oxygen from the lungs to the rest of the body (i.e. the tissues) where it releases the oxygen to burn nutrients to provide energy to power the functions of the body, and collects the resultant carbon dioxide to bring it back to the lungs to be dispensed from the body.

What does iron do?

Iron is essential in producing red blood cells.

Genetic testing at the McMaster Health Sciences laboratory was inconclusive – though they did raise the suspicion of sideroblastic anemia and that in the end this was their diagnosis of Kate’s anemic condition. Interestingly at this time, Dr.K was not convinced and wanted to discuss Kate’s case further with Dr.C (Kate’s metabolic doctor). He felt there were additional genetic tests that should be done now that they had the new information from Kate’s bone marrow biopsy. One area that Dr.K wanted to explore was thiamine (Vitamin B6) deficiency. If thiamine was not being processed properly in Kate’s body it could result in a sideroblastic anemia – and was also significantly linked to hearing loss.

Dr.K also noted the elevated alanine in Kate’s blood (it was at 680 when it should be at 0. Alanine was the elusive clue that to this day still confounds the medical team. (It’s been 5 years and we still don’t know any more about the persistently elevated alanine).

There were obviously still many more questions than answers. Again, there was a mountain of information to absorb and to share with the rest of Kate’s medical team. I continued to play the role of medical coordinator, following up with Kate’s pediatrician and faxing the test results to Dr.S, organizing therapy schedules, contacting the pharmacist about thiamine replacement therapy, and googling new medical terms so that I could keep up with what the doctors were telling me.

I took a look at sideroblastic anemia and got my first glimpse into what Kate’s blood looked like. (Not the prettiest red blood cells.)

S

Sideroblastic Anemia

Julie

Kate’s Story – Meeting Dr.C

When you journey with a medically complex and medically fragile child, you meet an unbelievable amount of doctors, nurses and therapists along the way. At my count Kate has been seen and assessed by more than 100. That is just a ridiculous number for a 5 year old, or for anyone one person, and I have to take a pause as I write this. It chills me, and adds to the weight of realizaton at how ‘special’ my little girl is.

Some of these doctors are ‘transient’ and in Kate’s life for only a brief time – taking no real interest in her other than to get her through the current crisis. Others are more engaged, having really connected with our family and taken the time and interest to get to know us as parents and Kate as a child – not just a case. These are the familiar faces of the CHEO hallways and in our community who stop and say hello – and ask how Kate is doing. Others are specialists at other health care facilities that are still champions of Kate.  And there are the doctors who are currently engaged directly with Kate’s regular care. At last count we were at 15 different specialists whom Kate sees on a regular basis between clinic appointments, admissions, regular community care and check ups, hospitalizations, and admissions. They are an incredible expert team who have come to work together in a collaborative way to care for Kate, manage her disease and her conditions, and to help us keep her safe.

One of these incredible specialists in Dr.C. I have to rave about him because over the last 4 years he has been an incredible doctor to Kate, and tireless and undaunted in investigating her disease.  This post is about our first meeting with him.

Meeting Dr. C

During Kate’s first hospitalization due to one of her episodes, she was heavily investigated by the genetics and metabolics team who were working collaboratively to find an underlying cause for the medical conditions that were starting to pile up. We initially met the team of residents for the group, who were obviously ferrying information back and forth from the lead physician whom we had yet to meet. We were still in a state of shock and really not understanding the various roles and hierarchy within the hospital. We weren’t demanding to see anyone, we felt relieved that someone – anyone – was looking into and investigating what was happening to Kate.

On the day we were discharged from CHEO – after a 10 day stay – we met Dr.C, one of the principle physicians in the metabolics program at CHEO. He was accompanied by his senior resident who we had met with several times during Kate’s admission and had provided detailed information about Kate’s health, her history, our concerns, and had taken several blood tests and tissue samples. Dr. C was now here to visit us and discuss their findings and what they thought might be happening to Kate. This would mark the first time we sat with a doctor and discussed mitochondrial disease. It would be 4 more years until Kate had a confirmed diagnosis. At that time ‘mito’ was just another condition that might describe the cluster of symptoms that Kate had. We wrote down the unusual name, and I am sure I must have googled it at some point, but it was not something that was used to describe Kate.

My mom had arrived to Ottawa to provide us support both at home and at the hospital. We were starting to flounder – I would say with reservation. We were exhausted and scared. We had a 1 year old who was very sick and in hospital, and a 4 year old at home who was being juggled between parents. We hadn’t slep in a year due to Kate’s constant crying, GERD, and issues with hypotonia and feeding, and we were just now getting the medical attention and support we had been desperate for.  My self employed husband was struggling to keep his new company up and running, and I had just come off of maternity leave and having not returned to work because of Kate’s health – I found myself no longer with a pay cheque. Friends were concerned for us, but not many people knew the extent to which our family had sunk it a major medical crisis. I don’t think I even recognized at the time the state we were in. I was simply trying to get through it – day to day. My mom was also an expert note taker – and a former nurse – so being free to talk with the doctors without constantly scribbling notes and questions was very helpful.

Dr. C started off by talking about the role of mitochondria in the body. That if these little parts of a cell were not working well, the body would have trouble making energy. He told us the metabolics team were in ‘middle clinical suspicion’ (on the fence) about whether or not Kate had mito.

Dr.C told us the tools to diagnose mitochondrial disease were very poor. There are 150-200 genes involved in mitohondrion functioning, and the most sophisticated test they had at their disposal currently was a muscle biopsy. Dr.C was reserved about muscle biopsy and said that it is really only helpful diagnostically if the ‘potential’ for mito is very high. He told us some mito biopsies come back normal even when the disease is present. His team had also sent Kate’s bloodwork away for microarray testing, and he estimated it would be 2-3 months before the results came back. Kate’s hearing loss was also another clue to the suspicion of mitochondrial disease and was being investigated genetically for a link – this testing would take 3 months.  We began to understand that a diagnosis would take time. For us, the muscle biopsy seemed like an important piece of the puzzle and we felt strongly about doing this surgical procedure sooner rather than later.

When I look back on this conversation and our subsequent decision – more like insistence – that Kate have a muscle biopsy as soon as possible, I realize what Dr.C was trying to do. He was trying to warn us and prepare us. He knew that a muscle biopsy may not give us the information we needed about Kate. I think he knew, even at that time, that Kate would prove to be a much more difficult patient to diagnose than the current tests that were available. As her parents, our first reaction was ‘Yes’ to a relatively minor surgery that may give us the information we needed to diagnose Kate. To us diagnosise meant treatment and treatment meant a cure – and we were highly charged in that direction as any parent would be. We wanted to get Kate better. We wanted her to be ‘well’.  We didn’t want ‘this’ to happen to her anymore, and now we knew there was something that might give us answers we wanted to do it.

Dr.C talked to us about Kate’s ‘cycles‘ or ‘incidents‘ – what we as parents were calling ‘episodes‘. Interestingly ‘episodes’ is the moniker that is being used to this day. I will also refer to her ‘episodes’ as her mitochondrial disease ‘cycling’ as we have days – weeks- sometimes months in between where Kate is episode free and doing well at her baseline. He talked about how these types of ‘episodes’ are common in children with mitochondrial disease.

We talked about a strategy to manage Kate’s episodes. We told Dr.C that to date we felt very alone an ill-equipped to help Kate. The strategy that we came up with was to have Dr.S, Kate’s community pediatrician to take the lead when Kate was unwell – or appearing with an episode. Dr.C would also communicate all tests and information this way. If things got worse or new symptoms presented, then Dr.S would call Dr.C to advise him and we would bring Kate to the emergency department where we would have Dr.C paged so that he could closely examine and monitor Kate during an episode.  We had no response either way to this plan. At that time we didn’t know any better about the ‘inner’ workings of a hospital, how triage worked, how Kate may be managed at emergency, or how acute her episodes could become.  Any plan, or sense of organized care for Kate, sounded good to us and so we left feeling like we were moving in the right direction.

In the next week, Kate had more bloodwork done and an EKG to assess her heart functioning. An echocardiogram was also done to provide a clear funciton of her heart – something that can be affected in many genetic diseases. To this day, Kate continues to have EKGs and echos annually as he rare from of mitochondrial disease causes cardiac myopathy. Something Kate is at high risk to develop. During that week Kate also had visual evoked potentials – basically an eye test to examine the functioning of her eyes. This test has been performed a couple of times and there has never been an issue.

We heard from the metabolics clinic and senior resident about Kate’s bloodwork and the progress on her various pending tests. A disturbing trend that they had noticed in Kate was an elevated metabolyte in her blood called alanine. This issue of persistently elevated alanine continued to be a problem for the first 3 years of Kate’s life. Combined with indications of reduced liver function and her episodes, the first mito condition of MELAS was mentioned to us. Instant googling from me, entered us into a world that I could never have imagined for our family. A world totally parallel to the life I thought we would have. The life I thought Kate would have. As we started to drill down into the possible conditions that might be affecting Kate and started to read more, we realized that our lives would never be the same.

Julie

Searching For A Cure

Mitochondrial disease has been in the ‘spotlight’ this week as Mitochondrial Disease Awareness Week continues. I was inspired by an episode of CBC’s The Current that I heard this morning (see below), and wanted to take a moment to highlight the significant role research plays in trying to find good treatment options or a cure for mitochondrial disease.

Mitochondrial disease is very difficult to diagnose.  At the moment, prevalence is considered somewhere between 1 in 4000 and 1 in 6000. Mitochondrial disorders can vary greatly in presentation, from mild to more severe symptoms, which complicates diagnosis.  It is also difficult to pinpoint because the science is not yet sophisticated enough to identify the disease readily or easily. The good news is that this is changing at a rapid pace. A few short years ago, when my daughter began having significant symptoms, a muscle biopsy was performed to try and diagnose the disease. Two to three years ago this procedure was considered the ‘gold standard’ for diagnosing the disease – and in some cases still is. Now genetic testing has become much more sophisticated and many researchers are moving toward this area of investigating the disease for diagnosis. In our case, axiome genetic testing was performed using the ‘mitocarta’* which is essentially an inventory of genes with mitochondrial functions. Since KK was highly suspected to have mito, it made sense to focus diagnostic genetic testing there and to see if indeed there were any ‘funky’ genes. Once identified, the most suspicious genes were then compared to my DNA as well as my husbands, and voila – diagnosis.  This took a full year to complete, but even that timeline is changing.

Mitochondrial disease is also a key area of investigation with some major and reputable diagnostic facilities. In October 2009, we took KK to the Mayo Clinic in Rochester Minnesotta. We were searching for a diagnosis for our child and had hope that a major research and clinical facility such as the famous Mayo could help us. We came away with the same information that we had from our Canadian doctors – KK had ‘probable’ mitochondrial disease, possibly a phenotype of MNGIE (a type of mitochondrial disease) but they could not prove it. However, when we left Mayo we were asked if we would allow KK’s blood and tissue samples to be part of a ‘biobank’ they were starting for mitochondrial disease. We decided we would, and now this Mitochondrial Disease BioBank at Mayo* has grown to a very significant global program.

Today on CBC Radio (I”m an avid listener), The Current had a very interesting program on IVF (in-vitro fertilization) to help prevent the occurence of mitochondrial disease in parents who have had affected children. Three person IVF is a form of mitochondrial replacement therapy. The replacement comes from inside the egg of a donor.  The researchers are now looking into conducting human trials.  It is controversial, but what inspires me is that this type of research is happening. Scientists are looking for a way to help families like ours – to help children like Kate live a healthy and full life.

As Mitochondrial Disease Awareness Week continues, my hope is that awareness builds among the public and interest continues to grow within the research community. I hope that one day when I am asked ‘what is wrong’ with Kate I’ll be able to say, “She had mitochondrial disease, but now she is cured.”

* Mitocarta  http://www.broadinstitute.org/pubs/MitoCarta/index.html

* Mitochondrial Disease Biobank – The Mayo Clinic  http://mayoresearch.mayo.edu/mayo/research/mitochondrial-disease-biobank/

* Three Parent In-vitro Fertilization  http://www.cbc.ca/thecurrent/episode/2012/09/19/three-parent-in-vitro-fertilization/