Finding peace (where I least expected it)

Last year I shared that we found Adelaide’s true diagnosis. To briefly recap: during Adelaide’s life, we never knew what was causing her multitude of symptoms. We had diagnostic names for her symptoms: epilepsy, hypotonia, mast cell activation syndrome. But we didn’t have a diagnosis to blame for them all.

Being undiagnosed complicated every aspect of her care. At the root, we had little hope for a successful treatment if we didn’t know what was causing her symptoms. As a result, we were left treating new symptoms as they popped up like a traumatic game of medical whack-a-mole. And while Adelaide’s condition was certainly rare, our frustrations were not. Roughly half of people with epilepsy don’t know the cause and one third never achieve seizure control. On a grander scale, according to the Mayo Clinic, 1 in 13 Americans suffer from a rare, undiagnosed condition.

The affects of not having a diagnosis went far beyond her medical care though. It meant we had no clear prognosis, no disease specific community to connect with, no way to know if future biological children would be similarly affected.

The first couple years of Adelaide’s life I was obsessed with finding her diagnosis. I scoured medical journals, flew Adelaide across the country to different specialists hoping one of them would have an idea, would have seen a child with Adelaide’s symptoms before. When we had exhausted the limits of commercially available tests we turned to research, and I enrolled her in the Undiagnosed Diseases Network (UDN), (full disclosure I now sit on the Undiagnosed Diseases Network Foundation/UDNF board).

The UDN which is largely funded by the NIH, was created to help patients on their diagnostic odyssey. Using a team science approach and testing that may not yet be available in a clinic setting, they commit to helping patients find answers at over a dozen sites nationwide. When Adelaide died and we still didn’t have answers, we decided to donate her brain to UDN researchers in hopes that someday science would catch up and provide us with an answer.

Last spring it finally did.

A gene called DENND5A was our likely culprit. In 2015, when Adelaide was born, very little was known about DENND5A. It wasn’t until a year later that research was published even associating the gene with epilepsy. Now, those same researchers, using samples of Adelaide’s brain along with biological samples from over 20 other patients, have published a paper explaining what this gene does and why variants in the associated gene can be detrimental.

I’m not going to pretend that I understand even half of the white paper that the researchers published. Fortunately, we have a meeting with our genetic counselor with the UDN in a couple weeks to break down the findings. However, I was able to contribute to a news article that was published shortly after the paper and in there they explain that the mutations “create disfunction, and this disfunction stops brain cells from dividing properly during development. The result is a developing brain with less stem cells, shortening the crucial time period that the brain forms as an embryo.”

Of course, I still have somewhere around a bajillion questions. But beginning to understand the basic mechanisms behind her brain and how they impacted her is bringing me more peace than I had originally imagined.

When we first learned that DENND5A was to blame, it all felt anticlimactic. I had a seemingly random grouping of letters and a number to answer the ‘why’, but still no greater understanding of the ‘how’. The answer I had been waiting for, yearned for, felt hollow. Miguel found solace in knowing that because her condition was inherited, we had done everything we could, that this was how she was made, who she was always created to be. I got there in time, but only after working through some guilty, griefy emotions first.

This information is different though. This is actionable. With additional research and time, a genetic therapy could be available for future patients. Realistically, we are years and years away from that, but these are the first steps, and Adelaide contributed to them.

I’m sure my positive emotional response to the study says more about me and how much I value productivity than anything else. Regardless, there is healing in that productivity. And a peace in continuing to find meaning in Adelaide’s life. A heartfelt thank you to this team of brilliant researchers at McGill University, who continue to work on DENND5A and to Nature Communications for publishing the study. Adelaide, along with her cohort, could still save the lives of countless other children with DENND5A mutations. Not today, not tomorrow, but someday.

I can’t wait to see it happen.

For those interested in further reading here is a link to the scientific white paper and the corresponding news article, as well as the Undiagnosed Diseases Network. I also created a private DENND5A Facebook group for anyone else out there with this diagnosis.

ID: A close up of Adelaide, age there, has her thumb in her mouth and is leaning back on Kelly’s chest. Kelly is wearing a red, white, and black plaid shirt, her hair is in a long braid, and they are both looking at the camera.