It had been nearly 7 months (Dec 2011) since our daughter’s blood was drawn for a genetic test to help determine if she has mitochondrial disease. The results of that testing just came back a few weeks ago and yesterday we had a phone consultation with a metabolic/mitochondrial geneticist who is helping us to interpret the results.
What the testing found and showed were 6 gene variants that are associated with Mitochondrial Disease. But, as was explained to us by the geneticist, none of these genes have (or have not) been tested or studied in a lab to prove whether they are disease-causing. In the genetics world, this is referred to as:
“Variant of Unknown Significance”
I have grown to love and loathe this term… for a family who is trying to figure out what is going on with their little one, it is increasingly frustrating to run a test that takes 7 months to get the results back only to find out that what was found may or may not be “significant” to your child’s health and well-being. My interpretation of Variants of Unknown Significance = ???????? is more questions than answers.
The geneticist did feel strongly that one gene in particular could possibly be explaining some of Lady A’s symptoms and “clinical presentation”, so she is helping us coordinate yet another blood test to determine the SIGNIFICANCE of the VARIANT OF UNKNOWN SIGNIFICANCE (VUS). Sounds crazy huh?? Well, if I had not attended the UMDF Symposium a few months ago, I think I would be much more frustrated than I am now. At the symposium I learned just how much mitochondrial disease is in it’s infancy. Some of the disorders and genes (especially nuclear ones) have only been identified in the last 10 years. A few years ago it was believed as fact that you could only get mitochondrial disease by inheriting it from your mother (via mtDNA or mDNA). In just a few short years, nearly 1500 genes have been identified that are crucial for mitochondrial function and thus disease that come from both your mother and your father (nuclear DNA or nDNA). This is the test which results just came back for our daughter, a test that looked at 400 of these 1500 nuclear DNA genes, inherited from both mine and my husband’s DNA. I also learned at the symposium that “studying a gene” and “reporting it in the literature” as “disease causing is not a simple as one may think. It can take YEARS of breading mice models and knocking out genes and seeing if a phenotype/genotype appears. One other point that I heard at the symposium that also stuck with me…is that this “variance” could be specific to only your family, so finding someone else on the entire world to publish a journal article on about the significance of your families variant may not be possible because it doesn’t exist or hasn’t been found in any other person on this whole earth!
In all of this I struggle and strive to look for the positive and the silver lining and the blessings… there are many, I just have to search… I am thankful that the test to confirm or deny the significance of the VUS is a BLOOD test and not a biopsy on skin, liver or muscle, therefore requiring NO anesthesia to obtain it (which we believe Lady A may be reactive to), I am thankful that Lady A is doing well, this is hard to say after just being in the hospital for the first time in her life, but she really is doing reasonable well considering the challenges she has had lately, and lastly, I am thankful that this testing exists and that we have found doctors who are able to help us interpret it and help guide us down this largely unknown path, one baby step at a time.
Onward and Upward, I am off to do a little more research and coordinate yet another blood draw for our sweet little gal, hoping that this vial will be the last, and that what they will find in it will be SIGNIFICANT enough to end the search for more VARIANTS OF UNKNOWN SIGNIFICANCE. No parent wants a diagnosis of a genetic, metabolic, mitochondrial, chronic disorder for their child, but with a diagnosis comes HOPE of being able to treat or use vitamin therapies to lessen some of the symptoms, and that is our HOPE for ‘lil Lady A, that we can make this path a bit smoother for her.