Genetic Testing - Update

Discussion in 'Fibromyalgia Main Forum' started by rockyjs, Nov 22, 2012.

  1. rockyjs

    rockyjs Member

    I haven't been active on the board for several years although I do still have the same symptoms. I developed chronic fatigue 40 years ago after a mono infection. But I just kept getting worse and eventually developed severe exercise intolerance and heart failure.

    Because one of my daughters also has CFS and fibromyalgia, I felt certain there was some sort of genetic component, but my doctors just weren't interested in pursuing it.

    A few years ago I was searching for something natural to treat severe neuropathy and came across some studies on Acetyl-L-Carnitine and R-Alpha Lipoic Acid. It did help the neuropathy, but it also started reversing my pulmonary hypertension (which is considered a terminal condition) and heart failure. My exercise tolerance began increasing, my immune system improved and my chronic anemia went away with no other change in diet or supplements.

    Because this was such a drastic change, I started looking into the genetic disorders related to carnitine metabolism. There were several mitochondrial diseases that were correlated, but when I showed everything to the geneticist at our university hospital, he refused to order any testing. Since I'm on Medicare the university has to guarantee payment for the tests, which can be quite expensive. Their budget has really decreased so children are getting priority. Most of these conditions manifest in infancy, but there are many that seem to be triggered by viruses or other factors in teens or adulthood.

    I finally contacted our children's hospital, and although they couldn't see me as an adult patient until I had a confirmed diagnosis, the counselor gave me the name of a fairly new company that tests for over 100 genetic disorders and the list included the tests I needed. These are actual DNA tests, not just screening. The individual tests I was seeking would cost about $2500 to $3000, but from this company the profile was only $349 for the ones I needed plus over 90 others. If you have commercial (non-government) insurance you're guaranteed price is only $99.

    I would encourage any of you who can afford this to get the testing done to rule out these disorders: It will also tell you if you're a carrier so it might be important for your children.

    If you can't afford the cost, you can request financial assistance:

    You will need to find a doctor in your area that is registered with Counsyl. Usually genetic counselors at children's hospitals (specifically maternal/fetal medicine) have names of reproductive specialists who are registered. Make sure you order the Universal Plus test so that you will be checked for MTHFR mutations and clotting disorders.

    I will be getting my results in about two weeks and I hope this finally ends the mystery of my lifelong battle with severe fatigue. You can either do saliva testing or a blood draw. The doctor who ordered it for me charged $15 for the draw. They filled out the information, put it in a kit that had a prepaid FedEx mailer, and I dropped it off immediately at the FedEx center here. You can access the results online when they're ready. After you get the results you can get a consultation with a genetics counselor and metabolic diet specialist (also usually affiliated with children's hospitals). In some cases you can get prescriptions for the dietary treatments.

    It is difficult to reach anyone on the phone. They prefer to communicate through email, so if you have a question that's your best bet. They do respond very quickly.

    This is not the same testing as the methylation cycle, although I believe there are a few tests that overlap. That is also an important potential genetic trigger of CFS.

    I hope this is helpful for some of you who still have no answers for the cause of your symptoms!


    [This Message was Edited on 02/11/2013]
  2. sunflowergirl

    sunflowergirl Well-Known Member

    Please post the results when you get it, and what you were tested for, if you want to share that info too.

    Will you then have an idea about your daughter?
  3. rockyjs

    rockyjs Member

    If I test positive then my daughter could also be affected and we will order the testing for her. I talked to one specialist who said they sometimes see three generations that are affected, even though most of the disorders require a mutation from both the father and the mother. Many of these affect enzyme activity and even carriers have some loss of functionality, but it usually doesn't cause symptoms. I believe external factors like pesticides, herbicides, certain medications, etc can further impact the loss of function.

  4. IanH

    IanH Active Member

    It is great you are doing this and I am sure your results will be of benefit to all with ME/CFS. The Japanese have spent a lot on this, so much so they call a subset of ME Carnitine deficiency disease. It certainly looks like carnitine deficiency is present in a subset of ME. This "deficiency" can occur for two reasons:

    Faulty energetics.
    Carnitine is synthesised from trimethyl-lysine derived from dietary proteins. The final step of the synthesis of carnitine occurs ONLY in the liver, . This synthesis is very energy dependant and so when mitochondria are not functioning well (as in ME/CFS) the carnitine is not being made enough.
    This low energy problem in the liver cells is typical of many "deficiencies" in ME, it is also possibly the reason why when many people get ill (not just ME) that vitamin D levels drop, ie not enough energy for the conversion to an activated form of vitamin D.)

    There is a concept in medical science called "triage" which means that the body preserves energy for immediate/essential functions and longer term functions are deprived. So when the energetics are not providing enough energy for even immediate needs these slower synthetic pathways suffer and we see deficiencies such as carnitine deficiency which can partly be overcome by taking a supplement or eating foods high in the deficient nutrient.

    Enzyme faults (Gene SNp)
    However the above does not preclude a genetic fault or SNp which could result in the absence of one of the enzymes such as trimethyllysine dioxygenase (TMLHE), 3-hydroxy-N-TML aldolase or 4-N-trimethylaminobutyraldehyde dehydrogenase (in the liver).
    Each of these enzymes (proteins) are produced by specific genes which should be in your test.
  5. Thank you for this helpful info... how much L Carnitine and Lipoic Acid were you taking?

    [This Message was Edited on 11/24/2012]
  6. rockyjs

    rockyjs Member

    I take 500 mg of Acetyl-L-Carnitine and 25 mg of R-Alpha Lipoic Acid. There are lots of studies of the combination for peripheral neuropathy. The improvement was gradual, but steady and I now had no nerve pain in my legs.

  7. This is all very interesting to me since I was told a couple years ago that I have 2 MTHFR Mutations and have often wondered if I should see a geneticist too. I do take 500 mg of L- Carnitine daily but wondered if I should increase to 1500 mg since I've read that some advise 500mg/3 times a day. Also, I've been taking the ALA but at a much higher dosage... 100mg/twice daily. So now I'm wondering if I'm taking too much? Right now I'm dealing with a bad bout of insomnia that started over a week ago... I feel like I'm crashing and burning lately I'm desperate to see any improvement... Sounds like this testing could def be worth pursuing...

    I will be interested to hear your results... please keep us posted.

    Thanks again, Jan....


    [This Message was Edited on 11/24/2012]
  8. rockyjs

    rockyjs Member


    You have to be careful about too much of any supplement. I usually buy capsules and only take part of one each day. I keep the opened ones in a pill container and have them labeled. It saves a ton of just have to be sure your hands are clean and very dry when you pull the capsule apart. Every once in a while one will fracture, but usually I can open and close them for two or more doses.

    You can actually create a deficiency of a nutrient from taking too much because the receptors decrease to compensate. ALA can cause you to feel a bit hyper, especially if you take it at night. That's true of many supplements. I make a green drink with mine using wheat grass juice powder as a base. I add a little D-mannose to help prevent UTIs and then my portions of various supplements from capsules.

    If you have two copies of an MTHFR mutation, then it's very important for you to use the converted form of folic acid, methytetrahydrofolic acid (also listed as folate). One copy causes you to lose the ability to convert as readily, but you can often get away with just taking extra folic acid (800 mg per day). But with two copies, your conversion is reduced 80%+ and you will have trouble with myelin formation and repair which can lead to MS, migraines, Alzheimer's, neuropathy, etc. In fact one of the main treatments right now for Alzheimer's is a high dose of folate. I use 50 mcg a day, but I only have one mutation.

    I wouldn't recommend more than 500 mg of carnitine unless you test positive for a carnitine deficiency or fatty acid oxidation disorder. It does suppress TSH production, so you have to keep an eye on your thyroid hormones including free and bound T3 and T4.

    If you're near menopausal age, you can pretty much expect bouts of insomnia for a few years. It just goes with the territory. I have had good success with small does of DHEA (no more than 5 mg per day) and black cohosh. My best insomnia trick is to watch YouTube videos on my cell phone until I get sleepy again. I've learned how to draw and paint, fix my computer, prepare delicious dishes, and speak Spanish. If I'm going to be awake I figure I'm not going to waste the time :) If you just lie in bed with the lights off and just watch videos on your cell phone, there's not enough light to overstimulate your brain and totally shut down melatonin production. You can put on a headphone to keep from disturbing anyone else.

    I've had to be creative to make it this far against all odds!


  9. ... for all the helpful info. Maybe I should take the ALA just once a day then... I've not tried opeing the capsules, but it sounds like a good idea... esp with it becoming more and more difficult to swallow all the pills I have to take.

    I do take folate (called 5-MTHFR)... can't remember how much right now since my brain isn't working so well due to being so exhausted. I may need to try the DHEA and black cohosh since I am at the age of menopause (oh joy)... I do take bioidentical hormones to mitigate the effects of menopause... but I'm sure that's impacting me some regardless. So thanks for that info...

    I also no longer have a thyroid due to thyroid cancer 14 years ago... they had to remove both sides... so I depend on Natural thyroid hormone for that... BUT my levels could all be out of whack... I know my cortisol def is... just haven't had any levels checked since June... just hope this new doctor is good and that I can get there so I can get my levels checked...

    But thanks again, Jan, for the great ideas and info... I really appreciate it! God bless you!

    Blessings and Gentle Hugs,
  10. glenp

    glenp New Member

    Please let us know the results. I feel that it it in my genes - my mom had it - I see symptoms in one son and the other was diagnosed adhd
  11. skychomper

    skychomper Member

    Thank you soo much for sharing this. I also have not been on the board in awhile, mostly because my success story was methyl b12 and I am much better now, and my CFS also started after mono. I'm back because I am very interested in the genetic component now, I just had a baby girl, who is 5 months today, and I'm delaying vaccines until I can make a decision one way or the other. If genes load the gun, I don't want a vaccine pulling the trigger. Also if I could do as you have learned, and supplement with what I need, If there is that need, i would love to feel even better than I do now. Recently had to be tested for MS because of troubling symptoms, but they are not present if I avoid gluten. Anyway, thank you, and keep us posted.
    Best of health!
    [This Message was Edited on 12/04/2012]
  12. glenp

    glenp New Member

  13. rockyjs

    rockyjs Member

    I got my results back from Counsyl (which is geared toward recessively inherited mutations causing disabling disease in children). None of the recessive disorders showed up, but I do have a mutation in the MTHFR gene which runs through my family and causes severe migraines and demyelination susceptibility. The treatment is to take the converted/active form of folic acid. There is a strong correlation to demyelinating disorders like MS and MTHFR mutations, especially if you have two mutations, one from each parent. The next step for diagnosing a mitochondrial or metabolic disorder for me will be skin biopsies to look for enzyme deficiencies. just lowered their price to $99. It covers more of the single nucleotide polymorphisms or SNPs that you would see in tests like Amy Yasko's genetic testing, although it does leave out two key enzymes related to sulfur metabolism. I just ordered that and will see what shows up. They also show your ancestry (x for men and mitochondrial for women), many traits related to inheritance and about 40 disease causing mutations. Many of the tests show a higher or lower risk factor for many conditions like Parkinson's, Alzheimer's, various types of cancer, etc.

    I hope some of you give the testing a try and see what shows up. If we compare notes we can help make progress in treatment based on patterns of commonly shared mutations.

    [This Message was Edited on 12/16/2012]
  14. ... for the update and the info. I am interested in doing the testing if it will help me to zero in on the best treatment for my particular set of health problems. I know that all of us with ME/CFS are different in the fact that we all have varying combinations of other health issues that impact this DD.... that's why I believe it's a mistake for doctors to ever try to treat patients with a "cookie cutter" mentality... but more often than not, this is exactly what they do, unfortunately. I do find it interesting that so many with ME/CFS have stated that this DD kicked in after a bout with mono. This is the same case for me, as well. So it sounds more and more like genetically, we are predisposed to getting this DD, and then the mono (or some other virus) is the catalyst that ushers it in...

    As I mentioned earlier, I have 2 copies of the MTHFR mutation and I know that one of my daughter's has only one copy. My oldest daughter has yet to be tested, but she has had relatively good health, in spite of having a mild case of juvenile rheumatoid arthritis when she was younger. My youngest daughter, however, the one we know has one copy of the MTHFR mutation, has had more health issues, unfortunately, and seems to have more in common with my early health problems. I've told her that she needs to take the 5-Mthf folate that I take, but I can't seem to get her to do it. She's in college and very busy and can barely remember to take a multi-vitamin every day. So I am most concerned for her, at this point. Although, my youngest son, who is only 11 years old, concerns me because even though he has a healthy appetite and eats really well, he is still skin and bones and can't seem to gain weight (I was the same way as a kid and so is my youngest daughter). He just doesn't look healthy, but he hasn't been diagnosed with any health issues. So perhaps I shoud get him tested too??

    Thanks again, Jan, for sharing all this. I probably won't be able to look into the testing till well after the holidays. But keep us posted. I'm very interested in comparing notes... I'm sure this has the potential to help all of us. Thanks again! And I hope you have a blessed Christmas!


    [This Message was Edited on 12/22/2012]
    [This Message was Edited on 12/22/2012]
  15. MicheleK

    MicheleK Member

    I have two mutations of MTHFR but I seem to do better when I take 300mg of Alpha Lipoic Acid twice a day. When I fail to take that dose my energy level just plummets into an even lower level than I already have with this severe form of ME. I also do better for a few hours after a dose of 250mg of Resveratrol and 100mg of Ubiquinol. I have had a couple friends try this combo when they needed to be somewhere for an hour or two and it has worked for them too. Anybody else found success with that combo? You have to make sure you have a high graded supplement as much of the Resveratrol on the market doesn't live up to what the label says is in the bottle.

  16. GBHope

    GBHope New Member

    I have 1 of the MTHFR mutations and no one is doing anything for mine. I'm wondering if I need to see a genetist too. Both my kids have health problems too, son and daughter.
  17. IanH

    IanH Active Member

    MTHFR polymorphisms are one of the most common genetic variations.
    Also it is isn't truly correct to call them mutations. Polymorphisms are variations to the gene structure, these variations are normal. Some polymorphisms are more prone to mutations than others and this can be a problem, especially when the protein(enzyme) which is coded is inactivated by the gene (as in Duchennes muscular dystrophy) or cannot be transcripted (as in Celiacs disease).

    The two most common MTHFR polymorphisms are known as C677T and A1298C. The frequency of these in the general population is around 25% and 13% respectively (ie 38% of people have either one of these polymorphisms). So even if you fall into the C677T group you will not necessarily have a problem with the enzyme synthesis ie with methylenetetrahydrofolate reductase (MTHFR) If a person has a mutation in this polymorphism this would by definition be rare and usually problematic. If would be necessary to take methyl-tetrahydrofolic acid approximately 800mcg daily.
  18. rockyjs

    rockyjs Member


    Everyone in my family with the C677T SNP has had migraines from a very young age. My daughter noticed that when she was pregnant they would go away so we thought perhaps there was a hormone connection, but we later realized it was because she started taking extra folic acid while she was pregnant and nursing. As soon as she stopped, they came back.

    When my grandson was about 5 years old the migraines were so severe they were going to do CT scans and use some very high-powered medications. At that same time my doctor had ordered the MTHFR testing for me and found a single copy of the C677T polymorphism. After reading more about it we asked the pediatric neurologist if he could try the folic acid (800 mcg). The studies used a much higher dose, but since that was the dose that helped my daughter we wanted to start with that first.

    Within a few days the migraines were gone, and the only time they return is when the supplement is stopped for a few days. The neurologist did a test on him, and he also had a single polymorphism. Since then several other family members with chronic migraines have started using the folic acid and it helped them, also. The doctor was so impressed with the results that she said she was going to check all her pediatric migraine patients.

    I realize it's considered a common SNP, but for some people it can have quite an impact. I think it's worth folic acid supplementation just to see. I use the folate form, but I was getting severe demyelination and it was much more effective than just folic acid.

  19. IanH

    IanH Active Member

    I am fascinated by the connection with migraine and the alleviation of symptoms using folate. My colleagues at Griffith University in Queensland Aus. did some research on this and did find that folates reduced migraine.

    Here is a summary from my Journal copy (sorry I cannot copy the original article, reported in Pharmacogenetics and Genomics (19:422-28)).

    52 patients with migraine/aura took folic acid (2mg. daily),
    vitamin B6 (25mg. daily) and vitamin B12 (400?g. daily sublingual) in a randomised double-blind trial. They achieved a two-fold reduction in migraine compared to placebo.
    The hypothesis was that homocysteine causes endothelial
    dysfunction and this triggers migraine when it occurs in the cerebral blood vessels. They also found that the effects were greater in those patients who have a folate-sensitive genotype, (as you do).

    You are also correct in saying that some people don't respond well to folic acid so the calcined form calcium folinate also known as folinic acid can be used. However you can now obtain the active form, methyl-tetrahydrofolic acid which is even better.

    [This Message was Edited on 01/01/2013]
  20. rockyjs

    rockyjs Member

    I received 23andMe results a few weeks ago, and over the weekend I plugged the raw data into a program that correlates some of the results with Amy Yasko's methylation testing and a detox analysis (

    This has really solved some mysteries for me...I had five different mutations in the Cytochrome P450 pathway which keep me from metabolizing drugs and toxins in the environment. I also had one mutation in the glutathione pathway and another in the n-acetyltransferase pathway. It takes a little footwork to figure out the significance of the particular mutations, but you can do searches on sites like PubMed on the mutation identifier and find lots of information.

    For instance one of the mutations I have is associated with the inability to metabolize polyvinyl chloride (PVC). That's why I have never been able to tolerate oxygen tubing and masks or IV tubing.

    I would highly recommend the testing for anyone with MCS. It will hopefully make your doctors take notice and realize it's not "all in your head!"