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.
