I’m Trying Not to Feel Discouraged by My Genetic Test Results

I eagerly kept refreshing my inbox.

My local doctor’s office had called about 20 minutes earlier, letting me know that it had received my genetic test results and would forward them to me via email. As I wrote in a previous column, I needed updated results to participate in any clinical trials for Friedreich’s ataxia.

I refreshed my browser once again. Still nothing.

The anticipated results would give me the updated counts of the number of GAA trinucleotide repeats on my FXN gene. As Friedreich’s Ataxia News notes, the sequence repeats between 5 and 33 times in most people, while the number of repeats ranges from 66 to over 1,000 in most FA patients. This inhibits the production of a chemical called frataxin, which is necessary for cells to function properly.

My understanding is that the fewer GAA repeats you have, the less severe your FA symptoms tend to be. Patients who develop FA symptoms later in life generally have fewer repeats than those who required a walking aid in childhood.

When I received a genetic test in 2001, my number of repeats was about 650.

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Twenty-one years later, I prepared myself not to be disappointed if the number had increased by about 20. I secretly hoped that my number of repeats had remained static, which would lead me to think that my physical therapy and personal training are having positive effects.

Finally, an email arrived. My eyes skimmed it, searching for a number. When I found it, my stomach dropped.

The test found between 853 and 963 GAA repeats. Not only had my number of repeats increased, but it did so by about 200.

I felt very disillusioned. I thought I was battling FA well, but now I questioned that. According to these results, my condition has progressed more than I thought.

Luckily for me, I know Layne Rodden, who’s currently a postdoctoral fellow at the Children’s Hospital of Philadelphia and will begin serving as director of patient engagement for the Friedreich’s Ataxia Research Alliance next month. I shared my results with Layne, and she offered the following insight:

“There are a few possible explanations for what’s going on here. One intuitive explanation is that your repeat length has indeed increased by 200 over the last 21 years. GAA repeats can increase over time, but the increase is typically small (~4 GAAs/year). This wouldn’t explain the increase of 200 GAAs seen with your tests.

“Another more likely explanation is that the difference between the two genetic tests has more to do with the technical aspects of the test itself. GAA repeats are not easy to quantify in the lab, but as technology and lab protocols/reagents improve over time, labs are able to measure GAA repeats more accurately. So maybe there has been some small increase in your GAA repeat count, and maybe the tests are more accurate 20 years later, perhaps a combination of both.

“But what does all of this actually mean for you? There is a correlation in which longer GAA repeats result in less frataxin and earlier age at symptom onset, however it is not a perfect correlation (or the only determinant of FA severity and progression). In a study we recently completed, we found that the correlation only works for GAA repeats up to around 700. People with GAA repeats larger than 700 did not have lower and lower frataxin levels like we expected, but they all had similar frataxin levels and similar ages of onset. This means that a person with 700 GAA repeats and a person with 1200 GAA repeats might expect to have a similar disease course. It follows then that even if your GAA repeat did increase by 200 triplets over the past 21 years, you could expect your disease course would be unaltered because your repeat counts are in that region where the ceiling effect occurs.

“You mentioned exercise, which is great for everyone, including people with FA. It’s unlikely that exercise ‘works’ by changing the number of GAA repeats or by preventing the number from increasing over time. In other words, GAA repeat counts are not an indicator of the benefits of exercise. Indicators that exercise is helping might include higher energy levels, improved well-being or improved use of your arms and legs.

“Overall, we should not conclude that your GAA repeat has increased by 200 repeats. And more importantly, this apparent change in your GAA count does not mean that you are battling FA poorly.”

Thanks for the valuable insight, Layne. Now I’m a little less discouraged. And with this updated genetic test, I’m now eligible to enter clinical trials. No matter what my number of GAA repeats is, Layne says it doesn’t mean I am battling FA badly.

Maybe she’s right. A little victory.

Note: Friedreich’s Ataxia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Friedreich’s Ataxia News or its parent company, BioNews, and are intended to spark discussion about issues pertaining to Friedreich’s ataxia.