Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
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MEGLATHERY MD: RCCX MODULE MAY EXPLAIN OVERLAPPING SYNDROMES

Discussion in 'General ME/CFS News' started by JaimeS, May 2, 2016.

  1. PennyIA

    PennyIA Senior Member

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    Just did a site-wide search for Dercum's... and found this thread and post.

    I was reading through the Dercum's symptoms as it's highly likely that's exactly what I have... and while I don't know if it's 'known to be associated with CFS'... what I can state is that a lot of the CFS symptoms are on their list... neurologic issues, mood issues, worsening symptoms with activity, crashes, etc... basically for me, the key components on Dercum's that make it a possible candidate diagnosis for me are the two out-lyers that aren't typical of ME/CFS....

    1) multiple clusters of onsetting/remitting painful lipomas
    2) frequent dislocation of ribs (not on the list, but other patients report they see it regularly and think it's caused by lipomas developing near the ribs)

    What I don't have is I'm not obese... but there are several patients on the forums that have this diagnosis that are also not obese... I'm about 25 pounds overweight (not obese, but overweight) and it does appear that the lipomas form where there is fat, but what it boils down to is that neither of the two above are common with ME/CFS.

    Now, what I really wonder is if there's an inter-related underlying issue which compounds ME/CFS with this (especially if you have a genetic tendency towards). OR if Dercum's is a precipitating factor and there's really two separate things... which without either being well understood yet is completely unanswerable with any amount of certainty.

    I just thought it was odd when I saw so many of the related ME/CFS symptoms portrayed under Dercums... probably the only thing I didn't see on the list was related to the frequency of POTs issues... which, is only optional under ME/CFS as it is depending on which criteria you use. Off to search if adiposis is on any other thread in case there's more people connecting dots between the two and using the other term for it.
     
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  2. Binkie4

    Binkie4 Senior Member

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    @PennyIA @stripey14

    Just to indicate an interest. Have no idea how I got reading this site.

    It could be describing my medical history. Diagnosed with ME in 2008, lipolymphadema in 2015 which brought me in touch with a Karen Herbst's work, was diagnosed with hypermobility and introduced to the idea that I may have Dercum's three months ago by an ME specialist. Earlier in life I was measured as having low progesterone and prescribed quite high doses. Am probably a HSP.

    I understand that members are concerned about non evidence based work, very
    sensitive to it. But " a shame to throw the baby out with the bath water". Curious about it. Liked " connecting the dots". @Penny1A

    It's 2 in the morning, am too tired to read more carefully and need to sleep, but wanted to register the interest and hope to return another time.
     
  3. wastwater

    wastwater Senior Member

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    Someone just shown me this,I forgot I posted on it ,maybe it's worth another look/think
    Foxc1 is close to this location on chromosome 6 that's where I located as important involves p450 still somehow
     
    Last edited: Aug 18, 2017
  4. perrier

    perrier Senior Member

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    A year has passed since Dr Meglathery posted here. I wonder what Dr Ron Davis thinks about her proposal. Any further news on her research?
     
  5. Binkie4

    Binkie4 Senior Member

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    @JaimeS

     
  6. JaimeS

    JaimeS Senior Member

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    @Binkie4 -- definitely can't speak for what Ron thinks in general, and specifically he hasn't mentioned Dr Meglathery to me. :)
     
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  7. Binkie4

    Binkie4 Senior Member

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    JaimeS likes this.
  8. perrier

    perrier Senior Member

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    From what I understand, she would very much like a chance to speak with Dr Davis. She does not think that ME is a psychiatric condition, by the way. I think it might be interesting for her to outline the genetic findings she has made.
     
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  9. stripey14

    stripey14

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    Hi,

    I was told that this thread had become active again and that it would be a good idea for me to update.

    Since I was last here:
    It has become clear that there is a high rate of autoimmune disease in patients with ME/CFS and their families. This can be explained by co-inheritance of C4 (autoimmune diseases) and CYP21A2 (acute stress response, enzyme to make cortisol, gene I posit responsible for creating danger response leading to CFS/ME) mutations of the RCCX module. The RCCX module is the only place in the genome where mutations are co-inherited and 10-20% of the population have these mutations.

    Naviaux has said that there is a psych profile associated with illness and CFS/ME is similar process to what is going on in autism.
    I have been saying this exact thing since early 2016. In fact, that's how the RCCX Theory came about. I believe that the psych profile results from the hormone milieu in utero and in infancy created by carrying CYP21A2 mutations, spiking cortisol with low basal cortisol and high androgens producing an androgenized brain. This psych profile involves a brain wired for danger and sharing qualities with babies born to women pregnant during the Christ church earthquake, exposed to spiking stress hormones in utero: sensory sensitivities, hyperfocus, exaggerated stress response, special abilities, outside of the box thinking and often better than normal stress reaction in most until illness occurs and physical symptoms start to happen at times of any sort of stress (exercise, infection, emotional, etc). The physical responses are due to high CRH, known to be associated with CYP21A2 mutations. CRH activates mast cells and turns on inflammatory cascades.

    There have been found to be 2 different populations of people with CFS/ME separated by immune response, comorbidites and cytokine profile.
    I posit that one group has CYP21A2 mutation(s) and the inflammation down stream from CRH alone and the other has C4 mutation(s) PLUS CYP21A2 mutation(s) and would have a high rate of autoimmune diseases and possibly hormonally based cancers (prostate and breast) in the family and all of the downstream effects of abnormal complement proteins.

    EDS is now officially linked with CFS/ME and Ron Davis's daughter has been diagnosed.
    TNXB mutations can cause EDS (considered to be a rare cause), but can also produce subtle findings of connective tissue issues (tongue tricks, flying bird with hands, popping joints, even all over stiffensss I have found to be associated with this psych profile and chronic illness. There are indications that TNXB mutations are rampant in the general population and co-inherited with C4 and CYP21A2 mutations. I have written to Ron Davis many times with no response-the first time in 2015 and this was after seeing subtle signs of this in both Whitney and Ashley in videos (I pointed this out in one of the packets I sent). More about that below.

    A GWAS study of the RCCX region demonstrated many of the RCCX comorbidities I have on my list and well-known to be associated with EDS (http://jmg.bmj.com/content/53/10/681). These include ankylosing spondylitis, psoriatic arthritis. Interestingly, my research partner, Karen Herbst MD PhD has seen a high rate of lichen planus in her adipose disorder patients (she is one of the top authorities on Dercum's-mentioned above- in the world), found with this GWAS study.

    Further, there was a big data study showing that many illnesses that I see running in the RCCX familes are related to each-other (running in the same families). https://medicalxpress.com/news/2017-08-big-yields-diseases.html

    Finally, I have had many people with the RCCX phenotype join my FB discussion group and in that group it has become clear that ion channelopathies are rampant, most people have subtle signs of connective tissue abnormalities, the highly sensitive/empath psych profile can become narcissism if the response to it is denial/shutdown. The psych profile overlaps with what is "known" about autism in some ways but not in others (can read people very well as part of danger response, I believe, but is socially awkward as the priority in the brain is to stay safe rather than make friends.) A very high percentage of the women have ring fingers longer than index fingers (indicating high androgen exposure in utero), a high rate of ambidext or left handedness, partially fused 2nd and 3rd toes.

    Also, by receiving emails from all over from all sorts of affected people, I have come to find that people with more rare conditions affecting cortisol production, like POR deficiency and CAH from 11beta, also develop ME/CFS.

    The RCCX mutations are very hard to study. Mostly, these mutation are not SNP's, rather they are highly complex and varied and not well characterized. Genetic testing with SNP targeting misses them completely. There are copy number variations and non expressing pseudogenes which need to be separated from expressing genes with extensive testing. Getting Ron Davis to contribute his expertise to this end has been my goal from day 1. Karen Herbst MD PhD and I have been gathering observational data for a year and have put together a state of the art questionnaire which is very detailed and will define this phenotype and will also create a rich dataset regarding diagnosis and treatment of a variety of associated chronic illnesses. The plan is to follow-up with questionnaire with extensive RCCX gene testing so that a diagnostic test can be developed which will not require genetic testing of individual patients (we have many physical findings, symptoms and psych questions to define this psych profile). We are writing the IRB Protocol now and will probably release the questionnaire in a month or tow.

    Trying to get in touch with Ron Davis has been very difficult. I wrote to him via snail mail, fax, email multiple times in 2015 and said I had this theory and wanted to speak with him. No response till spring 2016 when he wrote and asked for me to send the theory but did not give me a better address. This time sent the theory via snail mail, fax, email and was told by secretary that he had received it. No word back. Heard his daughter has EDS, so wrote again May 2017 with the whole theory, all the same ways. No word back. Karen and I met with Dr. Eric Gordon via Skype twice in June 2017 (the first time with me alone) to talk about the RCCX and our research. Dr. Gordon briefly met with Davis after the first meeting who told him that he hadn't received anything I'd sent. I contacted the secretary and sent again via email and requested confirmation of receipt. She told me he got it. No word. Dr. Gordon sent a summary not emphasizing danger response, the most important part, written by someone else which was not the ideal way to do this because danger response links with Naviaux's findings. No response. I watched the OMF symposium a few weeks back and heard Naviaux say there was a psych profile and this is the same process as autism (I sent him the theory in May 2017 saying this, no response). I then wrote to Linda Tannenbaum and sent her the theory. I received a response that Linda would present the RCCX Theory at the next research meeting. I haven't heard anything else. I am hoping that once the questionnaire is underway that we can make contact. Otherwise, we will hire a commercial lab. I have a bio-informatics company interested in looking at the data initially to show that there may be a signal worth investigating.

    That's the story. I hope that answers the questions posed...I typed this quickly between patients.
     
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  10. Valentijn

    Valentijn Senior Member

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    Perhaps you could answer the ones I asked earlier, due to concerns arising after perusing your website and your earlier comments on this thread:
     
    Last edited: Sep 12, 2017
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  11. perrier

    perrier Senior Member

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    There are folks here who work with Dr Davis, and I do hope that you, Dr Meglathery can get an audience with Dr Davis, ASAP. This illness is a horror show, and we need every medical doctor who is willing to get on board. I'm impressed by your eagerness to help, and I pray someone here will help you get together with the most wonderful Dr Davis. Please help, please. This illness is a viper.
     
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  12. wastwater

    wastwater Senior Member

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    Could you be in the right area but wrong locations I got it down to the top of chromosome 6 for myself
     
  13. wastwater

    wastwater Senior Member

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    CYP1B1 I have seen mentioned
     
  14. Ema

    Ema Senior Member

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    So is there any point in testing 17 hydroxyprogesterone? Especially if one has been taking exogenous progesterone? Would it being elevated point to (but not diagnose) RCCX processes?
     
  15. AngelM

    AngelM Senior Member

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    I found your RCCX study the first to address CFS symptoms in a way that makes sense to those of us who have experienced the illness over a prolonged period of time. The most puzzling aspect of this illness, and the reason it is impossible to accurately describe CFS health practitioners, is that the symptoms don’t make sense. But when you have experienced year after year of identical symptoms that appear in a predictable sequence, you begin to see a pattern emerging. And eventually that decades-old pattern cannot be written off as coincidence.

    I’m sure you have noted your website URL on this forum, but I’ve been unable to locate it. I believe in your hypothesis and would like to follow you and your partner on this journey. How can I best access your work?
     
  16. wigglethemouse

    wigglethemouse Senior Member

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    The website URL is in the first post on this thread - https://www.rccxandillness.com/
    Was this what you were looking for?
     
  17. Ema

    Ema Senior Member

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    There is also a Facebook group Dr Meglathery runs, RCCX and Chronic Illness Discussion. It’s a great place to ask questions.
     
  18. AngelM

    AngelM Senior Member

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    Yes, and thanks. I lose track of threads when they get too long.
     
  19. PennyIA

    PennyIA Senior Member

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    Just thought I'd share that I have a confirmed diagnosis now of Dercum's DIsease. Still trying to work full time, but it's rough. I've had to take short term disability a couple of times. And ended up having to use a wheelchair to work in the office one day last week (I usually work from home and don't need it).
     
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  20. bertiedog

    bertiedog Senior Member

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    I have just read the hypothesis of @stripey14 has written and I fit the picture completely. I am a carrier of CAH and when tested have had higher than normal levels progesterone even after menopause. I have needed cortisol replacement after menopause. I also waste salt in hot conditions.

    Also I am hypermobile in my arms and can easily touch my toes although I am 70. I developed ME/CFS in 2000 when I was 52 but it had been building for years and I was unable to deal with stress well as described. Both my parents were unable to deal with stress well so I can well believe some of what I experienced was in my genes!

    Furthermore I notice that she mentioned likely problems with cancer, both my Mum and brother developed cancer at 72.

    I think I better join the FB group!

    Pam
     
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