The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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What Differentiates ME from Primary Mitochondrial Disease?

Discussion in 'General ME/CFS Discussion' started by Rossy191276, Nov 17, 2017.

  1. Rossy191276

    Rossy191276

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    Given the advice that if 3 or more systems are involved that it could possibly be a genetic/primary mitochondrial disease it would seem that anyone that meets ICC/CCC criteria should try to rule out primary mitochondrial disease.

    But it seems from Ron Davis's and Naviaux's testing they don't believe there is anything wrong with the mitochondria themselves rather the mitochondrial disfunction is caused by something else

    I am wondering peoples opinions on what differentiates ME from known genetic mitochondrial diseases in terms of symptoms...

    Given that even though exercise intolerance can be part of PMD the fact that GET seems to be prescribed with primary Mitochondrial disease and there is no patient outcry from what I can tell perhaps extreme crashing from exertion in ME is one differentiating point.

    Would you agree or are there others you can think of?
     
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  2. vision blue

    vision blue

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    Mitochondrial dysfunction can be a cause of having "no energy" and excercise intolerance. But its not the only cause. LIkewise 3 or more systems can be mito as cause, but many other things as well.

    but agree if you can rule out (or in) mitochondrial disorders as a or the cause in ones particular case, then it makes sense to do so. Its one of many avenues that could be involved.

    there are different ways to go about it. If you suspect inherited based on other family members, and moreover, it follows a maternal inheritance pattern, then fully sequence thw mtdna. this is super easy to do and costs only about 150 bucks at ftdna, especially now with holiday sales. its true youd be testing buccal cells and sometimes heteroplasmic variants will only show up on muscle, but if its bad enough, it should show up in buccal cells to and certainly all simple variants will show up. the test fully sequences the entire mtdna, so you can rule out definitively lots of nasties.

    if other family members are affected, but not following maternal inheritance, then its a bit harder and one needs to look at genes in the nucleus that control the mitochondria. maybe exome seqeuncing, but worth checking first for what some suspected genes are that control mitochondria. exome testing still expensive at about 450 but you can get some bargains.

    if think mitochondrial dysfunction might be acquired, or just don't know the family history, then one can do something like the OAT test from Great Plains which includes markers of how well the mitochondria are working.

    btw, I've done all three of above tests.

    sometimes as we know with this disease answers arent' a simple yes or no. Also as far as I know, complete crashes can be caused by mitochondrial dysfunction, but can't site anything to "prove" that at the moment
     
  3. pattismith

    pattismith Senior Member

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    The difference should be given by a muscle biopsy . Reaction to exercise testing during two-three days may differ.
     
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  4. ryan31337

    ryan31337 Senior Member

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    I'm pretty sure that in some cases a MitoD crash from over-exertion can be far worse (in terms of clear objective abnormalities) than an ME crash.

    What I imagine going on is that GET in MitoD is prescribed with a lot more care and an understanding that more is not better. It is not prescribed in the perverted ME/CFS sense of pushing through symptoms to cure your false illness beliefs.
     
  5. pattismith

    pattismith Senior Member

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    Please, would you tell us the laboratory where you can have this mito dna test done ?
     
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  6. Rossy191276

    Rossy191276

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    The company is called family tree dna I am looking at it as well but just trying to get more research on the reliability of the buccal swab. I also had a muscle biopsy and my doctor said that there were problems found but the specialist said it was not mitochondrial so I am waiting to get the report to research more on those findings as well.
     
  7. pattismith

    pattismith Senior Member

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    Il you have your 23andme datas, you can already run it with the ENLIS Software.
    @BeautifulDay found her familial mito dna mutation this way, and after checking my own datas I found 4 missense mutations that may be related to my illness . This doesn't mean that it was present from birth however. thank you for the lab. name
     
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  8. BeautifulDay

    BeautifulDay Senior Member

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    One interesting thing that came out of the Mito Conference was the idea that every Mito Doctor speaking at the conference agreed that every MitoD patient should exercise, but never to the point of changing over from aerobic to anaerobic. One doctor said while most MitoD patients switch over to anaerobic way too early in exercise (or even just with an easy daily activity), some switch so quickly that they can't even catch the switch over during exercise testing. Just getting on the bike or standing on the treadmill sends some into anaerobic.

    The idea was to do something every day. One doctor gave the example of a patient that doesn't get out of bed, but lifts a can of corn every day. Some days it's more lifts, some days it's less. But overall the trajectory after 3 years is this person can do more than the patient previously could. More reps, more weight, more.....

    At the same time the doctors also agreed, listen to one's body. If you are more fatigued than yesterday, then don't push it to equal yesterday's exercises. You might be coming down with a cold or energy is being used for something else. It was agreed that patients listening to their own bodies and doctors listening to their patients is critical with regards to exercise.

    One study that came up three times by three different Mito doctors at the conference was the study on mice. A researcher had done a study on regular mice and also mice with a genetic mitochondrial mutation. Generally the normal mice (not MitoD mutation) have brown fur and are running around the cage at a certain age. The mice with the MitoD mutation have grey fur, aren't running around, and are much smaller at the same age. Then they had a batch of the MitoD mutation mice that they had workout on the treadmill everyday for 45 minutes. These mice almost looked like the mice without the mutation. They had brown fur and they were running around and over the mice with the mutation who hadn't exercised.

    When they looked in the lab at the mice, they found the mice with MitoD who exercised had a lot more mitochondria within their cells than the mice who didn't exercise. So therefore, while mice with MitoD produced less energy per mitochondria, if they exercised they produced more mitochondria which therefore increased the total energy production for each cell. Maybe not to the level of mice without MitoD, but it was more energy production. For people with fatigue, even a 10% boost in energy would be nice.

    I'll try to find the study or at least a slide from the conference.

    The take away of the MitoD doctors was:

    1) their patients should be encouraged to do exercise (they prefer switching up weights one day and walking or biking or dancing). A doctor did mention that weights combined with something else is the best they know of today, but could always be overruled by new studies tomorrow.

    2) their patients should be taught to do something they enjoy doing and will be willing to do. If the patient gets bored, then keep changing the exercise routine so it doesn't grow to be a chore.

    3) their patients should be encouraged to listen to their own bodies and to never push it when fatigued.

    4) their patients should feel and know that their doctor is listening to them (because each unique mutation and environment will impact what can be done and how often). Each patient is unique.

    5) their patients should be told about the switch from aerobic to anaerobic and how to recognize it and avoid it. Exercise by a MitoD patient into the anaerobic zone causes more harm than good. Laying up a mito patient all afternoon, or the next day, or a few weeks from one physical therapy session is not good. Exercise must be stopped before this point (before anaerobic) and it needs to be recognized in order to be avoided.

    6) Family members and physical therapists should be educated in order to know how important exercise is to MitoD patients, while realizing how quickly well intended pushes can lead to more harm to mitochondria (fewer mitochondria or mitochondria producing even less energy than they did before the exercise program).
     
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  9. BeautifulDay

    BeautifulDay Senior Member

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    Here are two slides presented at the conference. The mice in the top slide both have a mutation in the POLG gene that causes MitoD. While this is only one of hundreds of genes that can have a mutation causing MitoD, it's nice to see researchers digging into the field. Yep, we're still in the infancy in this field.

    Both mice in the picture have MitoD. The grey mouse that is not active didn't exercise. The mouse with the brown fur and that is active did exercise. They are the same age, yet the mouse that didn't exercise looks and acts much older. There were many mice in the study.

    POLG Mutator Mice.png

    POLG Mutator Mice Video.jpg
     
  10. BeautifulDay

    BeautifulDay Senior Member

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    Doing a Google search for "adeel safdar mice mitochodrial disease" brought up many interesting articles on related subjects. My Google searches will generally pull up studies first, since I read so many online. If your Google search doesn't do this, then search within Google Scholar instead.
     
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  11. BeautifulDay

    BeautifulDay Senior Member

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    I should clarify. When I was at the Mito Conference (not this latest one, but the one earlier in the year down south), I sat next to a mother and father who brought their son who is ill with MitoD. Their son is in his late twenties and is in a powered wheelchair and needed neck support, a feeding tube, hearing aids, etc..... Unlike my family, he does not have a hidden illness. In addition, while our family only needs the one mutation to have MitoD (dominant type - just from one parent). His type requires a mutated copy from both his mother and father to have his form of MitoD (recessive mutation requiring both parents to be carriers and give the mutated copies to the child).

    His mother told me how he never really recovered from last year when they brought him for regular physical therapy and the physical therapist kept pushing him to work harder and harder and harder.

    So while I'd like to think the information on MitoD and exercise and keeping it to a reasonable level for the patient and the importance of listening to the patient is getting out to the doctors and therapists -- it still has a long way to go.
     
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  12. Rossy191276

    Rossy191276

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    Thank you @BeautifulDay for such detailed information...

    I guess we hear so much information about what exertion intolerance and crashing looks like in ME which is so far proposed as mitochondrial disfunction caused by some other factor/factors than genetic mutations... it's good to get some information on what exercise and responses can possibly look like in genetic causes...

    I have my 23and me data but haven't put it through the software yet as was a bit intimidated by the process...

    Once I get muscle biopsy report I will try to find out more info about what the issues they found could be caused by or get a 2nd opinion as My doctor said the specialist said the biopsy does not indicate mito disease though they can't explain the abnormalities then I will likely look at it from there...

    I have one question for @beautiful day regarding time of onset... I am wondering with your experience now or whether it is discussed at conferences regarding likelihood of time of onset of symptoms...

    In my case my major symptoms are exertion intolerance, extreme muscle weakness in upper legs, core and chest (most likely diaphragm that makes talking difficult) and dysautonomia...but until aged 38 I was incredibly active and heathy running marathons, surfing and formerly a professonal tennis player training 6hr a day and had had no need to see a doctor for 10 years before onset...I had a sudden onset 2 years ago and a major crash from over-exertion 6 months ago has left me bed bound..it seems in line with ME sudden onset case but I am wondering if there are also cases of genetic disease where someone can go with no symptoms for so long and be so active without genetic mitochondrial disease showing up until age 38?
     
  13. ryan31337

    ryan31337 Senior Member

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    Hi @Rossy191276,

    Have you been screened for Myasthenia Gravis and related diseases?

    Ryan
     
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  14. Rossy191276

    Rossy191276

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    Hi Ryan....

    Thanks for your question. I have had extensive testing during 2 hospital stays in 2 of Brisbane's major hospitals. This included every test they thought could be possibilities including the autoantibody test for Myasthenia Gravis.

    Of all the testing I have had the 4 things they found are:

    • Abnormal EEG on the basis of fairly frequent runs of abnormal activity in left temporal region but MRI normal
    • Failed Spirometry Test—could not exhale enough air to register adequately
    • i was involved in the Melbourne Bioanalytics gene study which found that G Protein Coupled Receptor mutations were over 20 times more likely in ME sufferers than controls and I know i had a high number among the ME group but waiting to clarify with my doctor
    • And now an abnormal muscle biopsy from thigh muscles but reported by specialist to my doctor as not being indicative of Mitochondrial disease (this result has got me thinking about Mitochondrial Disease again)
    When I crash I do get many, many severe symptoms consistent with ICC/CCC but with enough aggressive bedrest and not talking most of the symptoms reduce over months to point where I feel almost normal when lying at rest and brain function returns and I can literally do as much mental exertion as I want but physical/emotional exertion is still extreme trigger with symptoms I mentioned in last post remaining
     
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  15. BeautifulDay

    BeautifulDay Senior Member

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    Yes, there are many cases of Mitochondrial Disease happening later in life. Here is a slide that a MitoD doctor put up at a Mito conference this past spring.

    Variation of Mitochondrial Disease cases seen by a Mito doctor.jpg

    You can see that MitoD symptoms can come on at any age. These initial symptoms vary significantly from one patient to another.
     
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  16. BeautifulDay

    BeautifulDay Senior Member

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    Often times, MitoD patients will look back and be able to put pieces (earlier symptoms) together after it's been discovered that they have MitoD. It's more what's the tipping point when the patient first sees the MitoD doctor to see if it's MitoD?

    Have you had the CPET test (exercise test - nose pinched, tube in mouth) to see what your level of oxygen uptake is and how quickly you switch from aerobic to anaerobic?
     
  17. BeautifulDay

    BeautifulDay Senior Member

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    In our family with MitoD, we know that if we overwork a muscle with an activity, we are going to have a crash with that muscle beyond what a normal person would. For example, our teen daughter used to sing in multiple choirs and in multiple theater productions every year. From overworking her muscles for years, she has vocal cord and diagphragm paresis (weakness) and gets multiple severe lung infections a year. We've learned when we work a muscle group and find weakness occurring, it's a good time to back off of that exercise or activity for a while. It's a warning that if we keep it up, there is going to be a major issue.

    In addition, as we get older (that is everyone, not just MitoD patients), our mito does not provide the same energy output. Therefore, if someone has a MitoD issue that reduces energy, let's say by 33% (not crazy bad, but still playing the game of life with one arm tied behind your back), then add in working a muscle group hard (so that the muscle has issues from digging into anaerobic often), and add that one is getting older and the mitochondria just aren't working as hard and providing as much energy as they used to. Under these circumstances, a crash is going to happen. Will the doctors in this example even look to MitoD as the cause? Maybe not unless one has a good MitoD doctor.
     
    Last edited: Nov 20, 2017
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  18. Rossy191276

    Rossy191276

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    I am too unwell now to have the CPET test. I am completely bed bound. I know that when in hospital I have close to 100% on the oxygen reading even when in severe crash but if I was asked to blow anything more than a normal breath (or a shallow breath when in a crash) I become too weak and also too weak to even whisper ( I went several months unable to talk at all)... but I have been in contact with several people who have become to weak to talk and in Ron Davis's severe study which included people who couldn't talk as far as I know the gene tests for MitoD were negative...
     
  19. Rossy191276

    Rossy191276

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    I am very sorry to hear that your whole family is suffering an grateful for your time. Since during my last hospital stay I had a muscle biopsy I am awaiting the copy of the report. My doctor has said that they found problems 'not indicative of mitochondrial disease' so when I get a copy I will look into what they found further...
     
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  20. BeautifulDay

    BeautifulDay Senior Member

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    I'm very sorry you are going through this.

    Every day, they are adding new mutations to the MitoD database. There is the possibility that a person may not show up as having a MitoD mutation this year, but may show up with a MitoD mutation as more mutations are discovered and added to the database.

    Do you know if Ron Davis' study did Whole Genome Sequencing (WGS) or Whole Exome Sequencing (WES) on the participants? If not, do you know what genes he was looking at? Or was it just the genes in the mitochondria which can only be passed to children from the mother? Did they give you your VCF files for the genes that they looked at? Was it blood or saliva or cheek swab? Sorry, I'm the geeks geek.

    At the spring MitoD conference, one of the MitoD doctors said that regularly he has patients that nobody can figure out and after reviewing their cases and symptom history he'll do the WES. What he has found on many occasions is that it turns out not to be MitoD, but various other genetic diseases that nobody thought to test for because they are so unusual. My hope is that doctors looking into MitoD are really looking for anything that would answer the question of "What the heck is wrong with me?", rather than just looking at the MitoD mutations known on that day.

    I'm a big believer in WGS/WES. Then as new mutations are then lumped into MitoD, one just needs to rerun their VCF file comparing it with known pathogenic mutations.
     
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