Our GUK1 Story
Guanylate Kinase 1 (GUK1) Deficiency is an autosomal recessive mitochondrial DNA deletions and depletions syndrome (MDDS). So what does that mean? Simply put, that my brother and I inherited a genetic mutation from both of our parents that causes our body to make “markedly mutated” mitochondria, which means our bodies don’t have the energy they need to function and stay alive.
08 - 13 - 1992
Born at less than 5 pounds, I spent the first couple months of my life in the NICU with failure to thrive. But seemed to do better once home with my family.
1992 - 2008
My brother and I had a very typical childhood - we both played sports and loved hiking. Our mild symptoms went unnoticed beyond my brother’s autism and NAFLD.
2008 - 2010
During my junior year of high school my brother was diagnosed with MDDS via a muscle biopsy. He went through the diagnostic odyssey with years of specialists and invasive tests - I owe him forever for this. My senior year, I was diagnosed as well.
2012 - 2014
During graduate school for genetic counseling, a research exome and some very smart minds proposed GUK1 as the candidate gene of our MDDS with subsequent functional studies confirming the theory.
09 - 04 - 2024
The paper on our family (and 2 other patients) was published in Annals of Neurology!
You may remember from biology class that the DNA in our body is written out in letters “dNTP” just like a book is, more specifically in four letters (A, C, T, and G). If you cannot write that DNA correctly, then you end up with more and more dysfunction as your body tries to function on a set of directions filled with errors.
The gene GUK1 is crucial in creating the letter G, so our bodies are essentially trying to write a book with 1/4th of the letters missing. This is what causes the “mitochondrial DNA” to end up with “deletions and depletions.” Without a fourth of the letters it needs to function, the mitochondria end up with less DNA than it needs (depletion) and the DNA it does have is missing chunks (deletions).
Hope Rises - A Possible Treatment
2024 - 2025
Forodesine, typically used to treat T-cell cancers, was identified as a potential treatment for our family. As a “purine nucleoside phosphorylase inhibitor” this medication prevents the body from breaking down the G basepair, hopefully allowing it to normalize levels in our body.
12 - 18 - 2024
Our team obtained “an expanded access, compassionate use, study may proceed” from the FDA for my brother based on his recent onset of heart failure.
I told myself when the drug was approved I’d dye my hair rainbow!
01 - 03 - 2025
Let the pre-trial prep begin! Updated echocardiograms, EKGs, pulmonary function test, vaccinations, and lots of blood work.
ETA brother starting in February!
02-2025 - 03-2025
Unrelated to the drug and with some bad timing, my brother ended up with aspiration pneumonia and in-patient for a month.
A couple nights in an ICU, kidney damage, and a NG tube later - we took an unexpected detour.
Bella (service dog) became a fan favorite for the hospital staff at least! Unofficial mascot and therapy dog for all.
04 - 2025
His out-patient team really went above and beyond to work with his in-patient team, coming by sometimes daily to check on him, and since I stress bake - cookies for everyone!
05 - 2025
My approval came through from the FDA and the hospital’s IRB!
05 - 09 - 2025
I took the drug for the first time today!
<— Treats for me
Treats for the staff helping with the trial —>
05 - 17 - 2025
Week one complete and my only side effects are a renewed love for spreadsheets and a path being worn into the carpet from doing 6 minute walk tests.
P.S. Tripping on a basset hound that’s very confused by you walking endlessly back and forth is a confounding variable that I hope makes it into any future publications.
05 - 26 - 2025
Almost 3 weeks on the medication and had my first noticeable side effect, but good news is - you can tell the med has made it all the way throughout my body, even into my roots!
J.k. but so far still so good!
05 - 31 - 2025
Still going strong - watching my white counts closely. Also wrapping up the last of my updated vaccinations (lost Hep protection from childhood, getting shingles, RSV, etc.) to try and be extra safe in case my white count does drop too low.
06 - 06 - 2025
One month in and a temporary pause. My T-cells have been trending down and finally dipped lower than my previous lowest levels so we’re holding the med a couple of days to see how they react. Fingers crossed they bounce back quickily.
06 - 19 - 2025
T-cells bounced back within 5 days but we kept me off of it for a full extra week to be safe. Restarted the drug today but with an every other day pattern - we’ll see if that keeps me from T-cell drops! Fingers crossed I don’t turn into a bouncy ball with my levels.
06 - 29 - 2025
Proud of my little T-cells staying level for the last 2 weeks while doing alternating days of Forodosine. Keep up the good work little friends.
07 - 07 - 2025
Questions I’m pondering this week:
How do you measure success for a mito treatment? (as if I can figure it out better than previous clinical trials)
With 6-minute walk and 30-sec sit to stand, will it just be the placebo effect?
Do number of naps count as a data point?
Am I having a good day or is my doctor measuring strength having a bad day?
If I tell my doctor I’m walking farther, will that extra-bias them in their assessments as this is unblinded?
07 - 20 - 2025
Many norms online for 30-second sit-to-stand testing are for individuals over 60 so I’m curious - how many can do you? Let me know in the comments of this post!
How to: https://www.cdc.gov/steadi/media/pdfs/STEADI-Assessment-30Sec-508.pdf
07 - 27 - 2025
Graduated to blood draws every 2 weeks and, more importantly, got to meet some 6 week old puppies!
*can you note the ptosis in this photo? #MItoMoment
