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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ATP Profile testing (UK)

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by BlissC, Nov 15, 2016.

  1. BlissC

    BlissC

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    Does anyone know of/had experience with a lab which accepts postal samples and does the ATP profile test for mitochondrial dysfunction at a cost that doesn't require taking out a mortgage to pay for it? The background to this is...

    I was diagnosed with fibromyalgia as a teenager 20+ years ago. I also have a number of long-term chronic conditions, including a rare neurological condition that affects how the body produces cerebrospinal fluid that I was diagnosed with in 2003, but assumed my increasing symptoms of muscle pain, weakness, and fatigue were worsening fibromyalgia symptoms, until I was diagnosed with ME around 18 months ago. The neurologiist said it was due to 'emotional trauma' and suggested the usual graded exercise and CBT. I've been down that route before with my fibromyalgia, and the exercise just made my symptoms worse, and counselling was a waste of time, as the only issue I have is that my worsening health is incredibly frustrating, as I can't do the things I want to do.

    One of the things the neurologist mentioned in his letter to my GP following the consultation, which he also copied to me, was that mitochondrial disease (not the same as mitochondrial dysfunction) needed to be excluded. He didn't give any clues though as to how I should be tested, where, etc., and after a protracted search my GP and I managed to find an NHS consultant with expertise in this area.

    It's a few weeks now since I saw the neurologist, and to be honest, the consultation was a waste of time. It was obvious that he'd made his mind up about me even before I saw him. He stressed that he'd requested information from doctors I'd seen previously. It seems that seeing a number of doctors in an effort to get appropriate tests, an accurate diagnosis, and some attempt at a treatment labels you as a hypochondriac, someone who needs counselling, and a waste of time for doctors treating physical ailments, but I'm sure many of you have similar experiences.

    He started the consultation by saying that he didn't think it was appropriate to test me for mitochondrial disease (even though I have many of the symptoms suggesting it). The testing involves a blood test, muscle biopsy, and genetic tests, and didn't even want to do nerve conduction studies. The excuse he gave for not doing the tests was that I'm on life-long warfarin as I have an inherited clotting disorder. I've had alsorts of things done while on warfarin, or I've temporarily stopped the warfarin and done injections of anticoagulants, and it's not been a problem. I've now self-tested, and self-managed my warfarin dosage for a number of years, and only last week had two toe-nails removed due to ingrowing toe-nails, and it wasn't a problem.

    At the end of the consultation the neurologist said he thought it was "unfortunate" that the neurologist I saw 18 months ago had mentioned mitochondrial disease, and said he thought "it would be very unlikely to have another rare neurological condition" in a way that suggested I was looking for something to be wrong. His conclusion was that my condition is a "functional disorder" - i.e. psychosomatic. As you can imagine, I wasn't in the best of moods after all that! Normally I get on well with doctors and I'm prepared to give them the benefit of the doubt. I know they're only human, and can make mistakes, and can't know everything. With this one though, from the start he made me feel as though I was a hindrance and what I had to say wasn't relevant. I came away feeling as though I'd hit a brick wall, and wasn't really sure what happens next.

    While I was trying to find someone with expertise in the area of mitochondrial disease I read Dr Myhill's book on mitochondrial dysfunction, and then of course found out that she's not accepting new patients. I do believe that there is some element of mitochondrial dysfunction in ME though, and I'm now thinking that I need to go down the ATP profile testing route. I had discussed this with my GP prior to seeing the latest neurologist, and she was happy for me to have blood taken at the surgery if I found a lab to do the testing.

    I've been in touch with Acumen labs, which Dr Myhill mentions, and they only accept referrals from doctors they already deal with. I've also been in touch with Biolab who offer a "CFS/ME Profile" which is £400+ and includes a variety of tests but doesn't include the ATP profile test. From the reading and research I've done, I'm convinced that there's a biomedical basis to ME, most probably mitochondrial, and given that the last neurologist I saw wouldn't do the mitochondrial disease testing, I'm thinking that mitochondrial dysfunction testing is logically the next step.

    My GP is happy for me to have blood taken at the surgery if I find a lab to do the testing. Does anyone know of/had experience with a lab which accepts postal samples and does the ATP profile test at a cost that doesn't require taking out a mortgage to pay for it?
     
  2. charles shepherd

    charles shepherd Senior Member

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    The MEA Ramsay Research Fund is funding, or has been funding, four separate research studies into the role of mitochondrial dysfunction in ME/CFS and how it should be assessed - including the expensive commercial test you refer to

    MEA funded research into the commercial mitochondrial function test:

    http://www.meassociation.org.uk/201...-further-mitochondrial-research-20-july-2015/

    The main problem here is that this expensive commercial test has not been validated by other independent researchers - which is why it is not used (and is normally dismissed) by NHS doctors who specialise in muscle and mitochondrial disease

    The results from the research we have funded are now being analysed, along with some further laboratory work which has been done on this commercial test by two other independent researchers. The results will then be submitted for publication. Once the results have been published, the MEA will be making a further statement on this commercial test.

    In our present state of knowledge, there is insufficient evidence to conclude that any of these commercial mitochondrial function test results are a reliable indicator of muscle or mitochondrial involvement or function in ME/CFS

    And if mitochondrial function needs to be investigated, especially to rule out primary mitochondrial disease - which can be misdiagnosed as ME/CFS, then there are 'Gold Standard' NHS tests available (muscle biopsy, MRS etc)

    So this is NOT a test that we can currently recommend or endorse

    MEA funded studies into mitochondrial dysfunction:

    www.meassociation.org.uk/2016/03/me-association-to-fund-fourth-study-into-the-role-of-the-mitochondria-in-mecfs-10-march-2016/

    I would add that I have a deep personal interest in mitochondrial dysfunction having used my own skeletal muscle in the first research studies (which took place in the 1980s) to demonstrate evidence of mitochondrial dysfunction in ME/CFS. The first research, which I did with Professor George Radda et al at Oxford, and involved magneruc resonance spectroscopy, was published in The Lancet. The second, which involved electron microscopy of mitochondria from biopsy specimens, was carried out by Professor Mina Behan et al in Glasgow.

    Dr Charles Shepherd
    Hon Medical Adviser, MEA

    Abstract from Lancet paper:


    1984 Jun 23;1(8391):1367-9.
    Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study.
    Abstract
    A patient with prolonged post-viral exhaustion and excessive fatigue (CS) was examined by 31P nuclear magnetic resonance. During exercise, muscles of the forearm demonstrated abnormally early intracellular acidosis for the exercise performed. This was out of proportion to the associated changes in high-energy phosphates. This may represent excessive lactic acid formation resulting from a disorder of metabolic regulation. The metabolic abnormality in this patient could not have been demonstrated by traditional diagnostic techniques.

    Acta neuropathologica electron microscopy paper abstract:

    Behan, W.M.H., More, I.A.R. & Behan, P.O. Acta Neuropathol (1991) 83: 61. doi:10.1007/BF00

    Summary
    We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.
     
    Last edited: Nov 15, 2016
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  3. Kati

    Kati Patient in training

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    Interesting. i had a muscle biopsy done for mitochondria DNA sequencing a few years ago, perhaps 3 years into my illness. I am pretty sure the report said I had slow twitch muscle atrophy. The DNA was normal, so the mito clinic dropped me.

    Re: getting a muscle biopsy done, I would probably suggest you wait a while longer, metabolomics might be quite helpful instead of an invasive procedure. As for paying for a private test- knowledge can be helpful but if nobody can understand the results or treat you, then you just blew the money...
     
    Last edited: Nov 16, 2016
  4. Hutan

    Hutan Senior Member

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    Welcome to the forum @BlissC. Good question and good answers.
     
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  5. trishrhymes

    trishrhymes Senior Member

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    Thank you @charles shepherd for the abstracts of the 2 papers. They are fascinating. I notice the second paper came out the year after I was diagnosed, but of course my GP knew nothing about it, and I was never sent to a consultant of any sort. I wonder how much attention the paper had at the time. It must have been about the same time the psychiatrists invaded our territory and took over.

    The saddest thing about reading these now is that it's 30 years on and still the British medical establishment believes the psychiatrists.

    And still we wait for a test.

    I'd go through the pain of a biopsy if anyone would offer one. I want to know if my mitochondria are malfunctioning. I want evidence. After 27 years of this, I want to have doctors believing me. I'm sure many of us feel the same.

    :cry::cry::cry::ill::ill::ill::bang-head::bang-head::bang-head:
     
  6. Cinders66

    Cinders66 Senior Member

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    I have had the acumen test few years ago which showed very low ATP production, which I think is what the game changing recent metabolomic studies by naviaux and fluge/Mella suggest? However my GP had absolutely no interest in anything outside nhs standards or uk cfs framework and I'm guessing all the test results would suggest to dr myhill would be her supplements which I have always felt possibly useful or possibly just stabs in the dark. As things stand, especially in uk, getting the evidence to support your sickness is difficult and neurologists can be the most infuriating specialists to deal with because of their functional disorders lazy categorization, which isnt really a way of approaching the illness from biomedical way , more behavioral focus from what I have seen.

    @trishrhymes I too find it staggering that in 20-30 years the mitochondria research hasn't been replicated one way or t'other

    @BlissC
    If you are new to The Murky ME world you might find it interesting to read up on the recent USA IACFSME conference where a lot of cutting edge ME Science was discussed. Might be good ammunition for future dr encounters too.
     
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  7. BlissC

    BlissC

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    Thanks guys for the welcome, the info and links.

    @charles shepherd - interesting article on intracellular acidosis. The tests the neurologist was willing to do was blood tests for creatine kinase and serum lactate.

    @trishrhymes - I know how you feel. I'm the same. I have to have facts and evidence. I'm a researcher by trade (mainly social research) and it's my natural instinct when I'm given a diagnosis of something to research the condition and understand it (the IACFSME conference is one that I've missed though - I'll take a look at that).

    There might not be a 'cure' for the condition, or a particularly effective treatment, but I do feel that with a chronic condition, knowing what causes it and understanding it are important in accepting it. In some ways, accepting a chronic condition and learning to live with it are like a grieving process - from diagnosis to acceptance you have to go through a number of stages. One of those is a need to understand - it's a form of fear. Fear is a lack of understanding - the unknown, and a lack of control. By understanding the condition, knowing what's causing your symptoms, while it doesn't give you any actual control, having that understanding, taking away some of the fear, is a step towards acceptance (but acceptance doesn't mean merely accepting the condition and having no hope for the future or for treatment or answers in the future).

    As @Cinders66 says, 'functional disorder' is a lazy categorisation. The problem is, once you have a diagnosis of a functional disorder, it usually prevents any further biomedical investigation. I'm very fortunate that my GP is understanding and open-minded, and usually happy for me to follow avenues of interest I've read about, such as agreeing for me to have blood taken at the surgery for tests and referring me to NHS doctors and clinics.

    I do believe that it has a biomedical basis, and given the reading I've done on the subject, I suspect there is some mitochondrial involvement. @Cinders66 mentions Myhill's suggestions for supplements. I guess though what I don't want to do is start taking supplements, not knowing if I really need to or not. I guess I could get my levels of various vitamins/trace elements tested, but it just feels as though, using scientific methodology as an example, like it's writing the conclusion and accepting the hypothesis without having run the methodology and got a result.
     
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  8. charles shepherd

    charles shepherd Senior Member

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    The good news, for those of us who have been trying (for almost 30 years) to get the medical establishment to accept these findings of structural and functional abnormalities in the skeletal muscle mitochondria, is that we are now in a position where some of this work has been repeated - and the study by Professor Julia Newton's group in Newcastle (summarised below) has been published.

    It's just a shame that it has taken 30 years to get this work taken seriously…..

    From Research section MEA purple booklet:

    5.3 Muscle studies

    A variety of muscle abnormalities have been reported (Arnold DL et al 1984; Behan WMH et al 1991; Lane et al 2003) that contradict the theory that muscle symptoms in ME/CFS are simply due to inactivity and reconditioning.

    Objective evidence of post-exercise fatigue has been demonstrated using repetitive isometric quadriceps exercise testing (Paul et al 1999).

    Oxidative defects in muscle energy metabolism – as demonstrated by magnetic resonance spectroscopy – may be due to impaired blood flow to the exercising muscles as a result of dysregulated autonomic control (McCully and Natelson 1999).

    And a case-control study has shown a shift in muscle fibre type from slow- to fast-twitch phenotype and concluded that muscle tissue is directly involved in the pathogenesis of some cases of ME/CFS (Pietrangelo et al 2009).

    It has also been reported that cerebral vascular control is closely related to skeletal muscle pH both at rest and after dynamic stimulation in ME/CFS (He et al 2013).


    Following on from the research carried out by Arnold DL et al (1984) and Behan WMH et al (1991), new evidence of abnormal muscle energy metabolism at a cellular level comes from a study using magnetic resonance spectroscopy (MRS) to evaluate pH (i.e. acid) handling during exercise (Jones DEJ et al 2010). The ME/CFS patients demonstrated significant abnormalities in the recovery of intramuscular pH, which appear to be related to autonomic dysfunction. The authors concluded that this is a biological abnormality that is potentially open to modification through disease management.

    The same research group, in Newcastle, have now assessed muscle bioenergetic function in response to three bouts of exercise with 18 ME/CFS patients and 12 sedentary controls undergoing assessment of maximum voluntary contraction, repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold (Jones DEJ et al 2012).

    The ME/CFS patients fell into two distinct groups: eight showed normal polymerase chain reaction (PCR) depletion in response to exercise at 35% of maximum voluntary contraction; 10 had lower PCR depletion. The ME/CFS group as a whole exhibited reduced anaerobic threshold heart rate, VO2, VO2 peak and peak work compared to controls. The ME/CFS group achieving normal PCR depletion also exhibited increased intramuscular acidosis, compared to controls after similar work, and a significant prolongation (almost fourfold) of the time taken for pH to recover to baseline.

    Some of this research taking place in Newcastle has been funded by The MEA Ramsay Research Fund.

    Attention is now also returning to the role of mitochondrial dysfunction in ME/CFS (Smits et al 2011) almost 20 years after Behan WMH et al (1991) first described branching and fusion of the mitochondrial cristae in 35/50 muscle biopsies and mitochondrial degeneration – swelling, vacuolation, myelin figures and secondary lysosomes – in 40/50 biopsies from patients with a post-viral fatigue syndrome.

    The MEA Ramsay Research Fund has been co-funding (with the Medical Research Council) a study into mitochondrial dysfunction at the University of Liverpool and an assessment of a commercial mitochondrial function test at Newcastle University. It is now funding a new mitochondrial function study at the University of Oxford. See section 5.10.
     
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  9. charles shepherd

    charles shepherd Senior Member

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  10. kangaSue

    kangaSue Senior Member

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    @charles shepherd , With there being a finding of excess of lipid, could this be indicative of a glycolipid storage disorder?

    It's not something I know much about other than it is a complex field involving motor neuropathy dysfunction with symptoms ranging from virtually non-existant to severely disabling but I see both of the patients with CFS included in the below study were found to have glycolipid antibody

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896049/
    [This study provides strong support for the long-standing observation by Pestronk and colleagues that a one-to-one complex of GM1:GalC constitutes a very sensitive antigen for screening MMN sera(Pestronk et al., 1997). Indeed, in this cohort of 33 MMN cases, all sera were reactive against the GM1:GalC complex in glycoarray screening, including those that were not reactive to either GM1 or GalC alone. In addition, 4 cases whose sera were negative for antibodies to the GM1:GalC complex by ELISA, were positive by glycoarray. These findings need to be viewed cautiously until the overall conclusions can be validated in other cohorts of MMN cases and appropriate controls. Although the 33 cases from our national area were randomly selected for inclusion in this survey, referral bias to both our diagnostic neuroimmunology laboratory and clinical service may have been a factor in increasing the proportion of antibody positive cases. The principle clinical point emerging from this study is that the diagnostic yield of the standard anti-GM1 antibody ELISA can be improved upon through use of the combinatorial glcyoarray

    Several other papers on the subject come to a similar conclusions as this paper;
    [The finding of antibodies to GM1 in complex with other glycolipids influences our ideas about the immunopathogenesis of MMN by providing further support for an antibody-mediated autoimmune hypothesis.]

    https://www.ncbi.nlm.nih.gov/pubmed/12429589
     
    Last edited: Nov 17, 2016
  11. charles shepherd

    charles shepherd Senior Member

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    Thanks for this interesting observation which I have not considered before

    My gut feeling is that the answer is no

    But I will take some expert advice here from one of our muscle research group (Dr Karl Morten) when I next see him
     
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