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.)

 

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