A Month of Anniversaries

I wanted to share this blog post this past Saturday. It was the actual 4th anniversary of being told that Kate was diagnosed with SIFD. (Things have been a bit busy since Saturday).

November is also notable for Kate being diagnosed with hearing loss – and needing hearing aids, followed by her diagnosis 2 years later as being completely deaf. November carries a lot of emotional weight for me.

But this is about SIFD…

Kate suffered for over 4 years with an undiagnosed disease that caused multiple medical issues, and medical fragility. In the midst of an incredible diagnostic odyssey that led us to visit four different major hospitals in Canada and the US, and have Kate’s blood and tissue flown around the world, in the fall of 2011, our family (Jack included) did a simple blood test as part of FORGE (Finding of Rare Diseases in Canada), a genomics project led by Dr.Kim Boycott. The purpose of FORGE was to examine undiagnosed children suffering from rare diseases and see if they could identify the disease through national collaboration of physicians, scientists and researchers. In our case, our metabolics doctor, Pranesh Chakraborty, went one step further and collaborated internationally with a team from Boston to identify the TRNT1 gene that causes SIFD.

I’ve always said that I was waiting for the huge SIFD announcement. The national or international recognition of an ultra-rare – and devastating – disease to have been identified. But the sharing of the SIFD diagnosis for the first child ever, happened in a small consultation room at the Children’s Hospital of Eastern Ontario with two parents, their trusted physician, and his notes. It was a simple conversation, both Brian and I had ‘donated’ the same shitty gene to Kate and the result was SIFD. Our children had a 1 in 4 chance of inheriting this previously unknown disease.

Genetics is helping to identify these diseases more and more, and a new/novel disease discovery just isn’t news worthy any more. I can tell you that for the 7 families with children living with SIFD, and the 20+ others whose children have died from SIFD, it is huge and the anniversary of knowing is very significant, so we ‘celebrate’ the discovery of SIFD with quiet and personal reflection about that day and that conversation in the tiny consultation room with our metabolics doctor.

I remember the moment we found out about SIFD very well. It is one of those emotional memories that you can physically feel as you recall it. I thought I would feel so differently. I thought knowing what was ‘wrong’ with Kate would change everything. That I would be maybe elated or excited that we finally had an answer. Instead, I felt empty and numb – and came to the slow realization that there was monumental mountain of the unknown facing Kate and our family, and that we still really had no answers to help her. Nothing had really changed.

So here we are on the 4th anniversary of the discovery of SIFD.  CHEO released this little blurb a few weeks ago about it.

Teamwork solves the riddle of SIFD

If it takes a village to raise a child, in research, it takes team collaboration. Teamwork and new perspectives can rocket discoveries forward and help make incredible progress. At the CHEO, we see progress every day that directly benefits our patients.

Dr. Pranesh Chakraborty, a metabolic physician and Director of Newborn Screening Ontario, and his team partnered with clinicians and researchers at CHEO, to determine that mutations in a specific gene were likely responsible for causing SIFD (sideroblastic anemia, immunodeficiency, fever and developmental delay) in one of the young patients at CHEO.

Dr. Chakraborty’s lab, with the help of Dr. Martin Holcik’s Molecular Biomedicine lab, was able to rapidly kick-start the needed research – something neither could have done alone.

As one team, they were successful in their quest. And in 2014 they proved their hypothesis that the cause of SIFD is mutations in a specific gene. Their success came from teamwork not just across CHEO, but across borders. The CHEO team joined forces with researchers in Boston and clinicians around the world to make this discovery.

Like modern-day Sherlock Holmes, these researchers are medical detectives examining the clues in our genes to identify those which cause rare diseases. This kind of teamwork embodies CHEO’s values, and allows doctor and researchers to expand the field of medicine, and in particular rare disease research, at the pace they do.

 

Here is what I would add to this short article:

“And thank you to Kate Drury, a brave little girl, who donated her own genetic material so that this discovery could be made. A little girl carrying the weight of a genetic discovery on her shoulders. A little girl whose family never gave up to find a diagnosis for her. One of only 7 children alive with SIFD in the world today and the only Canadian alive with SIFD.”

 

Julie

Kate’s Bone Marrow Transplant

Yesterday, Monday, February 16th Kate was to be admitted to the Centre Universitaire Hospitalier Ste.Justine (Ste.Justine) in Montreal for conditioning therapy in preparation for an allogeneic stem cell transplant. A bone marrow transplant (BMT) on February 23rd with her 10 year old brother Jack as the donor.

Remember my last post about decision making. This is the decision that has been made. It is the biggest decision of our life and it has been incredibly difficult to make.

I am writing this, and we are not at Ste.Justine. Kate’s BMT has been delayed due to unforeseen medical complications. It might be a good thing as the Ste.Justine team gets better prepared for her and the medical complexities that surround her. BMT is never straight forward, but for Kate is it even more complex. The protocol ‘checklist’ has to be edited and designed to be specific to her medical complexity. We don’t have a new date yet, but this breathing room has allowed me to write this post and to share some information about this journey.

 

 

 

Where it began…

Many of you who follow this blog, or who have visited Kate’s CaringBridge site know the history of her diagnostic odyssey, medical journey, and her ‘status’ as the first child diagnosed in the world with a rare form of mitochondrial disease called SIFD.

Once the discovery of SIFD occurred a small group of children were identified who were diagnosed with the same recessive genetic disease – about 15. Many of those children were diagnosed posthumously. But one child who was alive was doing very well, and was not suffering from any of the complex medical conditions the other children with SIFD were suffering from. That child had had such acute presentation of SIFD at age 9 months (specifically the sideroblastic anemia and inflammatory cascades), that he had received a ‘hail mary’ bone marrow transplant. And it worked. He has not suffered any further episodes, and is the only known case with SIFD who has developed neuro-typically.

And so began the conversation with us two years ago about considering a bone marrow transplant for Kate.

 

Imperfect information…

So we don’t have perfect information about the impact of a bone marrow transplant for Kate. We do know that to date 4 children have been transplanted worlwide for SIFD. 2 have survived and are doing well – with no further episodes, and 2 have sadly passed away as a result of the procedure.

We know that the BMT would stop the episodes Kate is having, it would cure her sideroblastic anemia and it should prevent further damage from the disease. But this latter aspect of the BMT result is not clear. Kate’s brain, heart, kidney and liver could still be impacted further post-BMT.

We expect a better quality of life for Kate post-BMT, but getting there will require a significant amount of sacrifice and suffering on her part. A bone marrow transplant is not an easy thing to go through. It is considered one of the most invasive and difficult procedures in medical practice. We don’t know if she will get through it (5-10% chance of mortality), or if there will be unforeseen consequences because of the bone marrow transplant (5%).

We do know, based on the ever-changing information and insight we have into SIFD, that without intervention, these children tend to die before they reach adulthood. They suffer a ‘catastrophic event’ characterized by an acute onset cardiac condition (cardiomyopathy) or an acute episode of inflammatory cascade that presents like an idiopathic septicaemia.

SIFD is progressive and it is degenerative. There is no escaping that.

What we don’t have is the crystal ball to tell us when this might happen.

We have been given a choice – and our medical team feels that the BMT is the best course of action to pursue. Our other choice is to live with SIFD and take our chances on Kate dying from this disease.

 

What is a bone marrow transplant…

There are a ton of websites dedicated to BMT. The one I like best is www.bmtinfonet.org

 

Jack’s role…

In an allogeneic stem cell transplant, a donor is required. Typically the donor is sought out from within the persons immediate family as a relative can offer a better ‘match’ and the better/stronger the match the less risks there are with the transplant. Sibling matches are considered the best.
Neither Brian or I are a match.
Jack is a perfect match for his sister. A 6/6 sibling match.

We are grateful that Jack has agreed to take on this role for his sister. He understands that his body is strong and he has something he can share that might help Kate. His first reaction was that he might end up with a ‘clone’ sister (pretty funny). We’ve described the process to him. The surgery he will undergo. How he will feel, and the impact it will have on him and his activities. As is his nature, he has accepted this role with little drama.

He is not a hero, but he is very brave.

I wouldn’t have expected anything different from Jack. He is an incredible boy and one of Kate’s greatest champions.

 

Kate…

I am lucky to have two incredible children. While Jack is brave, kind and empathetic, his sister is courageous, stoic, strong, loving and TOUGH. AS NAILS. She is a survivor. And she is one of the happiest people I know despite it all.

Kate will require 5-7 days of intensive ‘conditioning’ before receiving the transplant. To quote one of her doctors, they need to bring her to the brink of death and then bring her back again. Her intensive chemotherapy is needed to kill off all of her bone marrow to prepare her body to receive the transplant from Jack’s body.

The chemotherapy will be introduced through a central venous line (Broviac) that is inserted into a large vein above Kate’s heart. Because of the multiple blood draws, the infusion of chemo, medications, and the blood transfusions Kate will require, a central line is required to easily access Kate for these procedures.

Once Kate has finished the conditioning regimen (days -10 to 0), she will receive the transplant. This is a minor event I am told, but an emotional one, as the stem cells collected from Jack’s bone marrow are infused via an IV bag into Kate’s central line. The stem cells then find their way to the bone marrow space and start to set up shop.

Day 0 – Day 7 Are supposedly the most difficult. Kate will be very sick from the effects of the chemotherapy drugs and immunosuppression drugs. She will be on full isolation for close to 8 weeks. I can be with her, but will need to be gowned, masked and gloved at all times. Access to her and her room will be highly restricted.

Kate will lose her hair, she will have nausea, vomiting and diarrhoea, she will have sores in her mouth. The BMT team is ready to support her through all of it, and prepared to deal with any unforeseen issues that might come up.

Day 7 – Day 40 will be a period of waiting for engraftment – waiting for Jack’s bone marrow to take over and start to grow in place of Kate’s. Graft Versus Host Disease and rejection of the transplant are the risks during this time – as well as organ failure, bleeds, and infection. Kate will still be feeling unwell and recovering from the conditioning regimen and the transplant.

After 2 months – If all goes well and Kate is stable, she will be discharged to home. The first 6 months will be critical as wait for Kate’s T-cells to show themselves again. Until that time, Kate will have no functioning immune system and will need to be in isolation at home. Her nutrition and her hygiene and protection from any mold, disease, or illness are extremely important. A  common cold could be devastating. She will be required to wear a mask when she leaves the house and she will travel to Montreal and CHEO weekly for medications, assessment, medical management and follow up. We won’t be allowed any visitors into our home at that time.

Post 6 month – If all goes well, we expect Kate to be able to return to school and other activities. She will continue to be on several medications as her new immune system grows and gets stronger in her body, and she will be monitored closely. It will take at least 2 years for Kate to have a fully functioning immune system.

 

The Plan…

We are currently waiting for a new date for Kate’s BMT. Her bloodwork was poor last week and a surgery to install her Broviac could not go forward.

We are mobilizing friends and family to help us while Kate and I are in Montreal. We are grateful my parents have moved here for a few months to support us.

It is not clear what we need right now while in Montreal or when we are discharged to home, but we will be sure to ask as support will be welcome and much needed.

 

The path ahead…

It has not been an easy journey – these past 7 years. Having a child that is living with a long term chronic and acute illness that is ultra-rare has changed me / us / our family in ways many people could not even imagine.

Kate’s life, her journey, her diagnosis, have changed the lives of others.

That in and of itself is incredible. So much power and awesomeness that this little girl has brought to the world.

So the journey continues. And Kate will be awesome again. And she will help others to learn, and to live better lives and to not be devastated from the ravages of this disease.

That is not a gift I would be willing to give on Kate’s shoulders, but it is our reality. It is her reality.

 

I am grateful to the incredible medical team we have at CHEO and Rogers House, and for their guidance in this decision.

I am grateful to the team at Ste.Justine, and the international SIFD team for all the preparation they have done for Kate.

I am grateful to all of you who are following our story here, on CaringBridge, on Facebook and Twitter.

 

Life is hard – there is no doubt. And others have it harder – some easier. This is our place in life and we are challenged with making the best of it and living it the best we can and with as much ferocity and compassion as we can.

Go Kate Go! 

 

Julie

 

The Art of Imperfect Decision Making

A Recipe for Making Decisions

How to make an impossible decision in 7 easy steps 

 

Ingredients:

Information and Research

Gathering of knowledge from ‘the experts and specialists’

Analysis

Questions

Discussion

Weighing of Opinion

Pros/Cons

Evaluation of information

Decisiveness

Gut Instinct

Support

 

Method:

1. Gather as much information as you can through research. Mix this with knowledge and expertise from many sources (e.g. experts, specialists, others who have made a similar decision), placing an emphasis on those who are leaders in the area/topic on which you are trying to make a decision. Be prepared to search this information out internationally.

2. Mix all of this information, knowledge and expertise together and conduct an analysis by comparing and contrasting everything you now know. Where is the information similar, where is it contradictory, what are the gaps in your information, what other sources of information and expertise might be available, and find out what you do not know that you need to know. After this step in the process you can move to formulating your questions and identifying what more you need to know or who else you might need to speak to about your decision.

3. Your next step will require several discussions about the decision you are trying to make. The structure of these discussions will vary, and your recipe for decision making could include: 1 to 1 discussion, informal conversations with trusted friends/family/professionals, formal multi-disciplinary team discussions, discussions with specialists in the field. You might conduct your discussions over the phone, face to face, or over video-conferencing. You may also need to consider travel to other destinations in order to conduct your discussion in person. Consider the following when organizing and preparing for discussions related to your decision-making:

– Bring a friend who can listen and take notes. It is difficult to take all the information in when you are in a very important discussion/conversation. Having another person to assist in the task of listening and note taking can be very helpful to your decision-making process

– Ask if you can tape record the conversation. This can be helpful so that you can hear the conversation again.

– Prepare in advance. Write down a list of questions and concerns related to your decision and send them to the meeting participants in advance so that they are prepared to address them. (Sometimes sharing this list with knowledgeable friends or professionals in advance can help you to refine your list of questions).

– Bring a notebook and paper.

– Ask another person (social worker, nurse, trusted professional) to facilitate the meeting so that you can focus on the discussion and not on managing the meeting.

4. Analysis and Weighing of Opinion.

You will need time after the gathering of information and knowledge, analysis and discussion to weigh the information you have been provided with. A helpful tool  in this step of the Decision Making Recipe is to develop a Pros vs. Cons list and then to add a value or weight to each of the Pros and Cons. An example of this can be found here, Ottawa Family Decision Guide.

It might also be helpful in this step of the process to engage a Decision Making Facilitator or Decision Making Services, a third party who guide you through this process. This is particularly important to ensure there is open communication and that all parties of the Decision Making Recipe are working together and communicating well. In intense medical decision-making, this can sometimes get lost – this is where facilitated sessions can help.

Professionals can help guide you through the weighing of opinions and information, and can help identify where your priorities lie with respect to the decision you are trying to make.

5.  You may have to repeat Steps 1-4 more than once in order to feel decisive about your decision.  It is important to know that important decisions cannot be rushed, and you should feel supported in taking your time to make a decision.

6. Gut Instinct.

Your gut instinct needs to factor into to your decision-making. If it feels wrong, it probably is. In my experience, my maternal instinct has been referred to by our medical team and decision-making team, and I have been told to listen to it and factor it into my decision-making.

But what if your gut instinct isn’t clear? What if it isn’t saying anything at all?

I call this the vortex of decision-making. Circling and circling because the information, expertise, knowledge that informs the decision you are trying to make is imperfect and incomplete. How do you make a decision with imperfect and incomplete information? You make the best decision you can with the information you have.

The vortex of decision-making, also known as “indecisiveness” can be debilitating. It can eat away at your soul. It leads to stress, anxiety, possibly even depression and should be avoided at all costs. You avoid it by asking more questions, asking repeated questions, clarifying as much as possible and eventually coming to a decision, even if you are making that decision with imperfect information. A recommendation for your Decision Making Recipe is to set a timeline for making your decision (if one has not already been set for you). Living with an ongoing decision is very limiting and difficult. Once it is made you will find yourself ‘unstuck’ and able to move forward.  The decision can be changed, but at some point you will have to commit one way or another.

7. Once you have made your decision, sit with it. Let it absorb, start to live it and get as comfortable with it as you can. Shift your mind-set toward the decision you have made. Then push the ‘Send’ button and let the professionals know the decision has been made.

8. Once you’ve made your decision you will slowly need to start sharing it. Make it clear to others that you expect to be supported in your decision. Those that are not providing support need to play a more minor role in your life. They cannot contribute to the vortex of indecisiveness. They need to be ‘on-board’. Finding those people and giving the important role of supporting your decision is a last and most important step in this process.

 

Other Things to Consider:

– Others cannot and will not make the decision for you, but you can still directly ask your trusted team “What would you do?”

– Many decisions are imperfect because there is not enough information available or there is no obvious choice between the decision(s).

– Decisions can be changed/reversed to a certain point. 

– You should never feel pressured about making a decision.

– Include others in supporting you once your decision is made.

 

Julie

Note: Our family has been going through the process of a very difficult medical decision for Kate for the past 2 years. The Decision Making Recipe is based on our experience. We have made our decision  and it is imperfect and lacks all the information we need, but we are moving forward. 

I wish you the best of luck with yours. 

Anniversary Weekend – Part 1

Still waiting for our SIFD party

Still waiting for our SIFD party

 

Today is the anniversary of Kate’s diagnosis.

It’s hard to believe that three years ago today we sat in the office of Dr.C (you can read about Meeting Dr.C here) our metabolics and genetics doctor and learned that Kate has a new and ultra-rare recessive genetic disease that she inherited from Brian and I. It reminds me a lot of this article by Matthew Might, dad to a son who also has an ultra-rare disease and was also an N=1 (as I wrote about here).

To quote Matt Might:

If found my daughter’s killer.

It took over 4 years.

But we did it.

I should point out one thing. My daughter is still alive. 

Yet. My husband Brian and I have been found responsible for her death.

 

When we were told that they had diagnosed Kate, there was a moment for me – just a brief moment when I received the call to come in for a meeting with Dr.C to discuss our test results, that maybe there was something they could do for her. A moment of excitement (?)… No. That’s not the right word. HOPE.

The moment did not last. As Dr.C talked about genes and exome-genetic sequencing and recessive genetic this and that. I listened. But I didn’t at the same time. I knew that if they could do something for Kate. If this was something ‘common’ or least ‘known’. If the medical team could help her – they would start with that.

They didn’t.

We looked at graphs. We looked at stains of Kate’s actual genetic coding for the TRNT1 gene. We talked about genetic condons of GCT –  GAT – ATC and any other combination of those 64 triplets of nucleotides that make up our genetic code.

And then, Dr.C took a ‘picture’ of Kate’s TRNT1 gene profile and overlaid mine and the Brian’s. They matched. My heart fell into my stomach. I was trying to understand. Trying to nod my head in comprehension. Trying to be brave. Trying.

Kate has inherited the exact same mutation from Brian and I on the gene known as TRNT1.

It had never been seen before.

Our children had a 1 in 4 chance of inheriting this disease. A silent killer. Completely unknown.

Jack isn’t affected, but could be a carrier. We haven’t had him tested.

The mutation has caused a deficiency in the protein needed for this gene to do it’s job. That deficiency (variable) has caused an incredibly shocking cascade effect through Kate’s body – resulting in the multiple medical conditions and ongoing acute illnesses she suffers today.

To quote Dr.H (PhD), a researcher working on Kate’s disease. “It is hard to believe a deficiency on one gene could wreak so much havoc on the body”.

 

What We Know

Here we are, three years after our ‘diagnosis’ and here is what we know.

There are approximately 18 known cases of SIFD worldwide. After Kate was diagnosed, our brave Dr.C took a leap of faith and share the genetic findings with a physician he had been working with at Boston Children’s Hospital. Their collaboration led to the first cases being confirmed, and to the establishment of an international medical and research team that continues to work on SIFD to this day.
Their efforts have resulted in a paper that describes the condition of SIFD. You can read about it here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761334/

A description of the TRNT1 gene deficiency that causes SIFD was recently published in the Journal Blood (September 2014).

http://www.bloodjournal.org/content/124/18/2763.full.print?sso-checked=true

Here is a picture of how the mitochondria are affected by TRNT1 deficiency – making SIFD a mitochondria disease. (I’m still trying to understand it too. Sigh.)

 

F1.medium

Many of the diagnosis of SIFD in the patients referenced in the article were done post-mortem. These children tend to die in early childhood – under the age of 4. They were identified and tested based on the cluster of symptoms they had presented with.

To my knowledge, there are 5 children alive today who are known to have SIFD. Four in the UK, and 1 in Canada. Kate.

I have recently been told of 2 more cases in the US and Brazil, but am not sure if these children are still alive.

The children have a variable severity of disease. Ranging from severe to mild. Kate is considered moderate. The children are treated with blood transfusions if their sideroblastic anemia is severe enough, immunogloblulin therapy to treat the b-cell immungloblulin deficiency, many have tried Kineret and prednisone to ‘treat’ or control the episodes of fever or inflammatory cascades (with differing degrees of efficacy), all are hospitalized regularly and monitored for cardiac myopathy – a severe and deadly effect of the disease, and inflammatory cascades (or Kate’s Episodes as we call them), which can also be life-threatning.

To date, 4 children have received a bone marrow transplant (BMT) to treat the disease and curb it’s course.

The first child done was a ‘hail mary’ as his sideroblastic anemia and periodic episodes were so severe his doctors had no other recourse. His BMT was done before SIFD was even discovered. He is doing very well. No effects from the disease.

The second child died during the BMT procedure. She was also very unwell.

The third child is also doing well and had less severe form of the disease. He is off of any intervening treatments and not experiencing any further episodes.

The fourth child was transplanted just recently (October 2014) and there is no information about his/her status.

BMT is an option for Kate. A terrible, awful, terrifying option – but an option nonetheless. It has been offered to us.

The CHEO Research Institute, Boston Children’s, and the Manchester, UK Children’s Hospital are all working on different features of the disease.

I call them regularly asking them if they are any closer to a cure. They are not. They are understanding the protein deficiency better – and all the mice they give it to die. They know what needs to be fixed, they just aren’t sure how to do it. I’ve offered to bring Kate for a visit – to create enthusiasm among the research team – to introduce them to the  little girl behind all of these incredible efforts – to expose them to the genuine JOY that is Kate.

There is nothing more motivating than wanting to help her.

 

My hope is that we find more children like Kate and the others and are able to learn from one another to help facilitate better management of the disease – share our stories – support our medical teams in finding a treatment or a cure.

I am looking for ways to do that.

 

Julie

 

Falling Into Fall

I love the change of seasons in Canada.

I love the chill and coziness of the winter months. Cuddling under blankets, sipping warm drinks by the fire. Nesting inside our warm home while the snow flies. (I even love running in the snow).

I love spring. Shedding sweaters and turtlenecks for another year. Getting down and dirty in the garden. Loving the freshness and newness of the season and anticipating the summer months.

And summer – lazy days – a break from it all – a complete change in routine (both good and bad) – less time at CHEO – warm sunny days – cute little sundresses – flip-flops on my feet.

But fall is my favourite. Fall feels like the new year to me. It feels like the start of things – back to routine (yes, I like routine), cozy soups, cozy sweaters, the changing colours, a crispness in the air that requires just a little bit of bundling up, the warmth of a fall sun that takes the edge of a chilly fall day, getting back to activities for Jack and Kate…

 

Fall Leaves

 

Fall is a very significant season for life with Kate. Kate was born in October (2007). She was diagnosed with hearing loss in November (2008). She received her first hearing aids in November (2008). She was diagnosed as Deaf in October (2009). She received bilateral cochlear implants in November (2010). She was admitted for her first long stay at CHEO in November (2008). She visited the Mayo Clinic in October (2009). She received her eventual diagnosis of SIFD in November (2011). Kate started school for the first time in November (2012).

There are so many anniversaries to reflect on in the fall. It is an emotional and weighty season and it is a season of promise.

I wonder what changes, events, new milestones this fall with bring for us.

 

Julie