Widening the Scope of Investigation

Chronic Fatigue
If I look at my total symptom list,

  • Neuropathic- Multi-focal – pins, needles, loss of sensation, weakness,
  • Migraines:- Prolonged auras, vestibular symptoms,
  • Meniere’s Disease:- deafness, tinnitus, vertigo,
  • Respiratory:- Asthma,COPD, diaphragmatic weakness and Intercostal muscle neuropathy,
  • Cardiac Arrhythmias,
  • IBS,
  • Difficulties swallowing (intermittent and probably neuropathic – ie laryngeal palsies)
  • Unstable joints:- neuropathic,
  • Fatigue:- periods of unremitting tiredness after minimal exertion

I match the ME / CFS / FMS list almost in it’s entirety. But I don’t think I have that at all. Chronic fatigue, yes, but not syndrome, as I think it’s perfectly rational to think that HMSN amongst other things (Meniere’s, Migraine, IBS etc), is a great contributor to this. Just the physical effort of fighting against the ever changing weakness and loss of sensation, which seems to follow every activity I do, or at least those activities where repetitive movement, high impact strength or a combination of the two is required. Not only does this affect the muscles that are inefficiently innervated, but also the muscles that are needed to help compensate for this varying weakness. Then there’s the secondary strain on ligaments and tendons and the joints that they are attached to. Fatigue can be quite devastating after fairly trivial activity one day, and then bearable on the next, generally though I now need a longer recovery period. It makes it very difficult to judge just how much energy is available for any given task.

However, it might be that HNPP actually has a further complicating factor within the actual deletion itself. PMP22 is not the only gene affected in the deleted region.

For example. What about the effects of the COX10 gene? It is also disrupted by the HNPP/CMT1a mutation, in the case of HNPP there is one working copy, and one which has the last section of this gene deleted. With CMT1a there should be two copies plus an extra part of the gene. This may mean that the effects of this are more likely to manifest in those with HNPP rather than CMT1a… but I’m guessing…

COX10 is thought to cause a whole range of Mitochondrial diseases, which may well account for some of fatigue symptoms, and a large potential for far more besides. For it to be symptomatic, in a person with HNPP, other genes may need to be mutated. Unlike PMP22, COX10 isn’t thought to be a Dosage sensitive gene, and or environmental factors or other illness may be triggering factors. But it might account for the wide variability of expression for HNPP, or for as yet unrecorded and unknown phenotypes. If so the effects would manifest as wide ranging symptoms not necessarily confined to the Peripheral Nervous System (PNS). It is unlikely that this causes florid clinical disease, as these would have been previously noted, but it may have implications for the development of disorders such as FMS, CFS and ME, the diagnosis of which occurs rather too often in the HNPP community. There has been much speculation and hypotheses about the role of mitochondrial function and CFS, ME and Fibromyalgia, there have however been few medical studies to support this, but it is an evolving field of study, and it would still seem very possible that mitochondrial function might be a great contributor to these syndromes, at least for some people.

It’s also quite interesting that other CMT types have been found to be caused by other genes which have an effect on the function of mitochondria. One form of CMT2 has a mutation of the Mitofusin2 MFN2, and yet another form of CMT2 by the neurofilament light gene, which also seems to affect the mitochondria.
So it has been established that mitochondrial disruption in critial nerve cells, is a potential cause for neuropathy.
What about pmp22 and the other genes disrupted, duplicated or deleted with the common CMT1a / HNPP mutation? Is it possible that not only PMP22 is responsible for the neuropathy, is there some interaction going on that could be modified by other genetic (normally benign) factors, hence leading to a wide range in variability, and potentially other symptoms which are outside of the current medical model.

There is a study by Michael Shy and team, which would suggest that only pmp22 is responsible for the neuropathy of HNPP. So this would discount that the other mutated genes would have an effect on the neuropathy. But this research does not consider signs and symptoms outside of their pre-defined model of HNPP. They were only looking to confirm the known neuropathic aspect, not any other system wide signs and symptoms. And in the confines of this research it would seem to suggest HNPP can be fully described by the pmp22 deletion. That is an HNPP that only causes painless palsies, multi-focal PNS lesions in response to minimal pressure or mechanical trauma, and a diffuse length-dependent mild polyneuropathy.

However, it is my belief that the deletion responsible for HNPP has far wider effects that while not causing significant clinical disease, may affect many other body functions. However as these are outside of the neurological sphere of thought, they are usually dismissed or attributed to other causes. The division of labour, specialisms, impedes medical research. The patient will experience this as being bounced from one speciality to another, whilst important observations are lost, dismissed or discounted.

It was really quite startling but not surprising that in the recent British TV show, Britain’s Missing Top Model, that one contestant with HNPP also suffered from unilateral deafness, Blindness in one eye thought to be related to Migraines, and had a co-diagnosis of Myalgic Encephalopathy.

While physicians (Neurologists and Geneticists) continue to describe HNPP as mild in comparison to other HMSNs, further research and possibly cures and treatments not only for HNPP but for CMT1a and other CMT types will remain elusive. It is time to stop this arbitary ‘clinical’ selectivism and to start to study science.

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7 thoughts on “Widening the Scope of Investigation

  1. I AGREE HOWEVER WHAT ABOUT MULTIPLE CHEMICAL SENSITIVITY DISORDER – SAME SYMPTOMS AS FMS WITH SAME SYMPTOMS AS CFS WITHOUT THE PAIN-REITERATE CHRONIC FATIGUE A SEPERATE ILLNESS IF WITHOUG DIAGNOSTIC TENDER POINT PAINFUL MUSCLES (DR MARK PELLIGRINO AS FAR SACK AS 2001 WAS WRIING ABOUT THE SUB-SETS NOT NEC TO HAVE 11-18 TENDER POINT MUSCLES BUT MAY HAVE 7-24!). ONE CAN CONJUECTURE FOREVER – AS PART OF RESEARCH SOUTHERN AFRICA MUST SAY SO FAR THE CNS/ANS/ENDOCRINE/LYMBIC/PINEAL GLAND/HYPOTHALAMUS/LYMPHATIC/IMMUNE SYSTMS OF BRAIN AND BODY SHOWING MORE AND MORE GENETIC LINKS TO OUR FUNCTIONAL MEDICAL ILLNESSES (COX10 INCLUDED HERE). AS AN HOLISTIC CONSULTANT AND COUNSELLOR, CLIN NUTR, COACH, STRESS MNG, REHAB EXERCISE THERAPIST, MUST SAY I GO FOR POSITIVE THOUGHT AND INTENTION TO OVERCOME AND GO INTO REMISSION – RATHER THAN HARP TO PATIENTS ABOUT THE ‘WOES’ OF ‘INADEQUECIES OF ANSWERS’. TALKING NOW FROM 1 WHO IS IN REMISSSION OF ALL +ADRENAL FATIGUE WHICH GETS ME SOMETIMES BUT I SET MY OWN PERAMETERS TO ‘GET BACK TO NORMAL’ AND EDUCATE THIS WAY THOSE WHO HAVE BEEN, LIKE MYSELF, ILL FOR A V LONG TIME AND KNOW THE ONLY WAY IS THE ROAD LESS TRAVELLED AND MUCH HARD WORK WITHOUT STRUGGLING! SHARON LEVIN. fmssha@ibi.co.za

  2. Pingback: Recent Links Tagged With "mutation" - JabberTags

  3. I just wanted to say i have fibromyagia are you saying it could b the hnpp.. I feel my fibro is worse than the hnpp at this time.. achey muscles feel like i could scream..i see Jon wrote hnpp effects our muscles too…hmm i havent been up on hnpp in a while due to depression and i am in another depression and cant seem to get out of it…my brain is so powerful it tells me what to do…it will simply be getting up to pee lol…get a drink..take the dog for a walk oh my that is another thing. i notice when i dont walk him i feel worse..started having legs gving out due to sciatica and it was i wasnt walking dog as much and then i started again and now it went away..well, jon i hope to keep in contact not like five years go by…i look forward to the readings and i just wish i could understand more what u are saying..little confused at this point..well take care all and god bless feel better peace…grace

    • Hi Grace, it could easily be that you have both, HNPP and Fibromyalgia. I think it’s possible that for some people HNPP might be involved in causing a secondary fatigue syndrome, It might not be the only thing that triggers it. However, a lot of people with HNPP do seem to suffer from fatigue.
      I do wonder though whether there might be some other gene involved with the deletion that in some cases does trigger the fatigue syndrome. The truth is I don’t know. It’s only speculation on my part… sometimes my speculations can be a bit ‘off the wall’ and perhaps not really that helpful.
      Whatever the cause, if it’s recognised there might be some ways to treat or manage it.

  4. Not sure if this is still going. But if my comments can help someone out there, here goes:

    When I now look back at my life I can recognise the HNPP affecting my life, pressure palsies that took ages to recover, loss of feeling in little fingers, back of my scalp etc. At 50 I was diagnosed with HNPP after issues with my left leg (foot drop) after a motorbike crash. Until then I had done nothing to try to minimise the effects of HNPP (how could I, I did not know I had it). In fact you could say I had lived a life doing the opposite. And I had always been fit and never short of breath.

    I had become single parent with 4 boys at 46 (youngest 6 months old) and they became my focus. I did not sleep more than 4 hours per night, I worked two jobs and studied on top of taking care of my family fulltime. I did not have time to do much about my fitness. In fact I neglected it. (I am slim and no extra weight). I then got a demading management position that I have now held for 5 years.

    But now the fatigue has started to set in. I quickly get short of breath, I get tired walking up steps and have to stop. My sex drive has almost disappered. I still ride motorbikes, but after a few hours in the saddle I am tired. I will still do 5 – 6 hour nonstop rides. But then it will take a few days before I am fully functioning again.

    Initially (for a few years now) I have fought the fatigue by using energy drinks. I have often tried to stop using them, but after a couple of weeks with much less energy and my brain functioning at a lesser capacity, one drink and I again feel revitalised. And so I again start using them. Reasoning that why not use them as I know that I function better with them than without.

    But I also realise that part of the problem is that I am not fit. So I have setup a fitness gym in my house and have just started using it. X-trainer, rowing machine, multi gym. As young I used these on regular basis, and so I have a good idea what I do. I have started slowly where I do not push my self too far. The plan is to increase the activity every two weeks. I will monitor my pulse and the improvements I make and I will try to update here.

    The main reason I am going down this track is to try and fight my increasing fatigue. As it currently affects all parts of my life (work, sex, my lack of patience with people, activity etc.) I think I will be able to monitor, in a non-scientific way, my progress.

    The only thing I am worried about is the repetive movement that is proven to cause onset of HNPP episodes. I am hoping to learn where the limit goes and how far I can go.

    As mentioned, I will update here approx two weekly to coinside with the increase in the activity.

    Wish me luck!

    • Good luck Pete. My experience with the gym has been knowing when to rest, recognising the first signs of over-doing it, and I didn’t find that easy. It may be that I was well out of shape when I started, having been afflicted by the inner ear disease for quite some years my fitness declined quite rapidly, then, not knowing I had HNPP, every attempt to get soem fitness back ended in further periods of inactivity due to the over use aspect of HNPP. The only exercise which I found helpful was Taichi chikung, the shibashi 18 step routine, The teacher was very good in explaining the principle of soft-limit, ie knowing when to back off as soon as tension is felt. Unfortunately, I’m rather lazy and haven’t kept it up, perhaps this is a wake up call!

      Thanks for your comment, please do give some updates during your fitness program,
      cheers,
      Jon

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