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

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

 

How Did This Happen?

There has been a story out there in the news media for close to a year now about a young girl who was seized by the state children’s protective services in Massachusetts after a medical disagreement between parents, doctors, and two different hospitals. The Justina Pelletier story.

As with any story that has been filtered, and the details are not all there – citing privacy and confidentiality issues. But the details that are available tell a chilling story about abuse of power. A child with a condition that is not well-known or understood, a disease that has no standard treatment plan or cure, and a lack of consultation with her treating physicians, can be taken from her parents, taken off all of her current medications and treatments, and kept in the psychiatric unit of a hospital with little to no visitation with her family or friends, and the parents accused of medical child abuse.

Horrifying. Terrifying.

 

My visceral reaction is disgust at the doctors and staff who did this to this young girl and her family. I am astounded that there will be no repercussions to any of them for the trauma they have caused this young girl and her family. But my instinct kicks in, and despite the questions I have about what these doctors were thinking, and how could they do this, I start to think of our own situation.

Rare. Unknown. No standard treatment. Many specialists involved. Many medical institutions involved.

I wonder if this could have happened to our family when we were searching for a confirmed diagnosis for Kate.

Could this happen to other children who are rare, without a confirmed diagnosis, medically complex, medically fragile, or perhaps to parents who are not savvy about how to ‘behave’ within the system.

I am a strong advocate for Kate. I feel that I am part of her medical care team and have an equal voice at the decision-making table. I voice my opinion. I appreciate the doctors opinions, but I also take into account my own knowledge and expertise as the expert on Kate. That is patient engagement and patient and family centred care right? Am I naive about the rights that I have to make decisions as her parent?

What makes the Justina Pelletier case hit home for me is that Justina has mitochondrial disease. A disease that few know about, where little research is done, where donation dollars and support don’t flow, where the medical community is still learning, and where there are few experts.

How does something like this happen?

How could the system change so it doesn’t happen again?

 

Julie

Mitochondrial Disease Awareness Week September 15-21, 2013

Mito week

MItochondrial Disease Awareness Week is September 15-21, 2013.

It’s a time for mito to be recognized, to raise awareness, and often a time for many fundraising events for mito to be held as well.

Mito is suspected to affect 1 in 6000 people. Mitochondrial diseases are difficult to diagnose and there is no treatments or cure.

I’ll be messaging (on FB), tweeting @solidfooting and blogging (here) about mitochondrial disease this week. I’ll also be changing my porch light bulbs to green ones – LIght Your Porch Green – in honour of those living with mito and those that have left us. I invite you to do the same.

Here is Kate’s mitochondrial disease story as told on her Caring Bridge site:

At 4-6 months of age, I started to notice that Kate’s motor development was behind and that she did not seem to be paying attention to sound or making normal baby babbling noises. She was not reaching typical developmental milestones for her age and was still very floppy, as a newborn would be. Kate was also experiencing other health issues such as chronic anemia and episodes of unexplained illness and fever. I also noticed that she did not appear to be responding to my voice or to sounds from her baby toys. The first few years of Kate’s life she cried all the time and she barely slept. My days were spent holding her and trying to console her the best I could.  Our GP did not seem to have any answers for us, and was at a loss of what to do.  Several trips to the emergency department only resulted in long waits and being sent home with little information, or investigation, and no change in Kate’s status.

When Kate was 9 months old, at the urging of a pediatrician friend, we engaged a consultant pediatrician to help us begin a broader investigation into Kate’s health.

In November (2008), Kate was hospitalized at CHEO for ‘irritability’, fever, and cyclic vomiting. This was the fourth time Kate experienced the symptoms which we have come to call her ‘episodes’ . It was during this hospitalization that an intensive examination of Kate began diagnostically.
The ‘episodes’ began in June 2008 and have increased in frequency and intensity.  The pattern is typically the same;  vomiting, intermittent fever, she stops drinking and eating, discomfort/pain, irritability, extreme lethargy lasting 7+ days. She has very little strength or energy and is unable to perform the skills that she usually does, like walking, talking, eating, It takes Kate 1-2 weeks to ‘normalize’ after a typical episode. The acuteness of these episodes began the investigation and diagnostic odyssey into Kate that lasted over four years. Kate has been hospitalized countless times and has undergone many invasive tests – MRI, CT, bloodwork, urine, lumbar puncture, gastric tests, ultrasound, x-ray, muscle biopsies, bone marrow aspirate. She has become a human pin cushion.

On November 7th, 2011, Kate was diagnosed with a rare form of mitochondrial disease called SIFD. Sideroblastic Anemia, Inflammation, Periodic Fever and Developmental Delay. This is a recessive genetic disorder that has no treatment or cure. To date there are only 15 known cases, 4 of these children (including Kate) are alive today.

At 13 months, Kate was diagnosed with permanent sensorineural hearing loss caused by her mitochondrial disease. In February 2010, after symptoms of additional hearing loss, it was determined that Kate’s hearing loss has progressed and is now severe to profound in both ears.  After very careful consideration due to complications from anesthetic, Kate received bilateral cochlear implants at the Hospital for Sick Children in Toronto in November 2010.  The implants were activated at CHEO on December 13, 2010. She is undergoing intense therapy to teach her to listen and speak.

Since 9 months of age, Kate has had more than 30 ‘episodes’ requiring multiple hospitalizations.  Kate has been seen by doctors at The Children’s Hospital of Eastern Ontario (CHEO), Sick Kids in Toronto, McMaster Health Sciences Centre, and The Mayo Clinic in the US.  Her blood and tissue have been studied at research institutions around the world. We have experienced what the medical literature calls a ‘medical odyssey’. Kate is also responsible for the diagnosis of several other children, bringing closure to other families who were searching for a diagnosis.

Kate is now part of the Coordination of Complex Care pilot program at CHEO to help coordinate her care and better manage her episodes.  She is also a palliative care patient at Rogers House.

Kate’s medical condition includes: – Global developmental delay – delayed myelination on MRI – Sensorineural hearing loss (profound) – Cyclical vomiting + and hemodynamic instability with episodes of unexplained fever, illness and pain – Sideroblastic anemia – Nephrocalcinosis and hypercalciurea  – Chronic constipation – Immunodeficiency (Hypogammaglobulinemia) – Post-anesthesia complications – Spinal syringomyelia (syrinx) – Osteopenia – Pili Torti – Ataxia – Weakness and Fatigue

When Kate is feeling well she walks independently, she loves to ‘swim’ and go to her gymnastics class. She loves to go on bike rides, riding behind mom in a trailer. She is communicating with gestures, sign language, and a few words.  She attends kindergarten at our local school thanks to the support a one on one educational assistant, and resources that allow her regular rest periods.

Many of Kate’s days are compromised by severe fatigue. We manage Kate’s energy by limiting her exertion and conserving the energy she does have. Kate cannot walk long distances and she uses a stroller to get around (soon to be a wheelchair). She wears and AFO brace to steady her right leg, and on days when her ataxia is particularly bad, she will wear a helmet to protect her.

Kate also has wonderful periods of feeling ‘well’, where her disease seems to be less aggressive and where her physical abilities and energy seem more typical. These are wonderful days, and we are excited when they stretch into weeks or months.

It is sometimes exhausting to relay Kate’s story as it is complex and ever-evolving.  We are keeping family and friends updated on her health and diagnostic situation via our journal entries on this site.

Thank you for visiting and for your well wishes, support for our family, and positive thoughts and prayers for Kate. She is a beautiful, loving, intelligent and stoic little girl, and deserves the best this world has to offer.

Julie, Brian, Jack and Kate

N=1

beach solitary

 

Walking alone – trailing my feet through the sand – feeling the sun on my back – letting the ocean lull me, calm me.

Alone with my thoughts – pensive. Taking a moment in time – this unexpected, unplanned, unanticipated, unwanted time – to breathe, consider, exhale.

Enjoying the solitude, and then realizing. I am alone.

JD 2009

 

As you may know from reading this blog, Kate has a rare form of mitochondrial disease called SIFD, which stands for sideroblastic anemia, immune deficiency, fever, and developmental delay. At the time of diagnosis, after an incredible diagnostic odyssey, Kate was N=1. Within several months of sharing the information about the recessive genetic disorder that causes this disease, 14 more cases were found, spanning the last 20 years. Only 4 of those children are alive, including Kate and none are in Canada.

Although mitochondrial disease is the broader diagnosis for Kate. Being diagnosed with a mitochondrial disease is similar to being diagnosed with ‘a type of cancer’. There are many different types of the disease under this very broad disease definition. Finding out who you are and what your mito is within that broad description is something only few mito families ever achieve.

When you are a parent, whether of a disabled child, a child with an acute illness, or a typical child, you seek out community. You naturally gravitate toward the park, playgroups, coffee shop seeking the moms like you – getting little sleep, carrying a baby, worrying about typical baby and toddler issues. Parents of children with medical conditions need this community even more, and support groups and very strong advocacy groups have started out of necessity to get important services in place, but also as a means for families to connect, share their stories, support one another in navigating the health care system, and support one another in navigating and understanding their child’s disease. It is group think. It is parallel thinking rather than going it on your own, and it is important to families survival and ability to get through the ‘dark’ times they will inevitably have.

I remember the early days with Kate, the first 2-3 years of feeling absolutely isolated. Struggling with her health issues, navigating the beast of our medical system – mainly alone, trying to stay on top of her ever evolving medical conditions in the absence of a unifying diagnosis. I wanted and needed a community to connect with. I wanted to share with another mom the struggles I was going through, to get advice, to learn from what they had learned, and to have a shoulder to lean on if it was there. Within the first 18 months and into her second year we had a social worker assigned to us, but it was clear her role was mainly to assist with funding related questions and less about supporting us.  The isolation I felt was difficult for me. I am not an introverted person, I still hung around with my mom friends in the school yard, and would share what was happening with Kate, but none of them could relate. They were sympathetic and offered words of support, but they were not living it, and could not understand what I was going through. (To be honest, I wasn’t even sure what I was going through).

 

What I really wanted was another mom (or dad) whose child had the same disease as mine and not knowing what disease my child had, I felt that would never happen for us.

 

When Kate was finally diagnosed with SIFD, I was excited. We had crossed a threshold and there was now possibility of better understanding how to treat her acute episodes, research could get started to look for treatments, a cure might even be possible at some point since the gene that causes SIFD had been identified. I was looking forward to connecting with other families, hearing their stories, reaching out, and sharing information about how their child’s disease was managed. For many reasons, this did not happen. None of these children were in Canada, the one other child who was died within a short time of being diagnosed. Some of the families did not want to connect, and physicians weren’t always great at facilitating families getting in contact. This all changed for me in April 2013 when I received a phone call from a Canadian doctor. He had a child he had been treating, who has SIFD, and he wanted to speak to us.

I was stunned, and excited, and hopeful. This was the first time a doctor had reached out to us personally, and not through our medical team. He explained to us that this child had suffered undiagnosed for over a year, the child had been sent to the NIH (National Institute of Health Rare Disease Program in the US) for further investigation. At the very end of the visit, just before returning home, a doctor who was aware of Kate’s case saw similarities and considered the same diagnosis for this child. After genetic testing, it was confirmed that this child also had SIFD.

What then transpired was what I had been searching for, a family to connect with. The family wanted to connect with us, they wanted to share stories. We emailed several times and had one long phone conversation, sharing our experiences about our children, remarking on similarities and noting differences. Their child’s disease was more severe than Kate’s and as a result different interventions were being tried. Our medical team learned from those experiences and as a result Kate’s acute treatments changed. I could now say, “the other SIFD family”, and even though we were now only 5 families worldwide, I somehow felt like we were part of a group.

A few weeks ago, after a brief email silence, I heard from the mom. Her child had passed away due to complications from SIFD.

I was stunned. Heartbroken for her and the enormity of the loss of her child.

I rationalized that her child had a more severe form of SIFD, but nonetheless I can’t help but think of how and when this disease will further impact Kate’s life. I felt fear and shock and a deep sadness.

I feel alone again. At the same time, I feel even more determined to reach out to the other 3 SIFD families try again to share with them and establish some connection. Not a connection about mitochondrial disease, hospital navigation, special needs, medical fragility, schooling, therapy, deafness, funding, special equipment etc. I have built up that community in spades, and am grateful to the friends I have in those communities.

I am grateful for the gap they fill for me, for the frank understanding they have of the life we lead, and the compassion they have for the things still to come. For what they share with me. Thank you to those reading this – you know who you are.

I still feel the need to have that connection to SIFD, for others who have Kate’s disease. Who can talk about the treatments they have tried, the research underway, and the uncertainty of this disease. To see myself reflected in their journey. To share that bond no matter how tenuous.

 

Julie