Great chart Rich ....and just to think that in 100 years time, people will look at this chart against a similar chart of the future and say, 'wow that bit is so wrong ' chortle chortle ....and then notice all the extra complexities that by then will be known! We won't be there of course - good thing too or we could be very embarrassed!!
Rich I have some problem understanding these 'partial blocks' which you so often talk about, with the implication, that they are causative to our M.E./CFS/FMS problems or as being stand alone causes. Am I misreading you? Do you mean these 'blocks' are causative to our health issues or are you saying that they are an effect of something else which has 'upset the apple cart'?
How do the 'partial blocks' start if they are not congenital? Surely if they are not congenital they need some triggering factor to cause their onset with their subsequent disarray leading to pathophysiology. A fundamental interfering factor must happen to cause the cascade of change. Why couldn't this precipitating cause or interfering factor be a Retrovirus for instance? (I'm choosing an RV over and above toxic exposure, Lyme, Enteroviruses etc but it could be any of these external interferences).
I, for instance have 21-Alpha Hydroxylase Deficiency. This is caused by genetic mutations (autosomal recessive) which produce an enzyme block in the steroidogenic pathway. Symptoms in most cases, except for very mild cases, are apparent early in life.
Now for me the enzymatic block is not the cause of my condition, it is the effect of two faulty mutations. If the body is such a well oiled machine then everything that goes wrong must has a cause. I fail to see then, that the 'partial methylation block(s)' of which you speak arises spontaneously and do(es) not have a cause external to itself!
You may ask, "does cause matter" if the symptoms can be significantly improved?
In the case of my 21-OHD, the answer is 'no'. The cause cannot be changed at this point in time ie. the genetic mutations cannot be altered. But if M.E./CFS is caused by something that can be treated, and that's why I chose an RV, (as many of the other theorised causes have been tackled one way or another with little success), then getting to the root cause where fundamental change can take place should be the desired goal!
Perhaps I view things way too simplistically
I think you are right on.
You may not have seen a writeup of my complete hypothesis. The original 2007 ppper can be found here: http://www.aboutmecfs.org/Rsrch/GSHMethylation.aspx
An explanation that I wrote in response for something more readable can be found here: http://www.aboutmecfs.org/Rsrch/GSHSimpleExplanation.aspx
These are still pretty up-to-date, though I have modified the hypothesis a little as I learn more from published research.
In reponse to your specific question, yes, my hypothesis proposes that the root cause of onset of ME/CFS is a combination of a genetic predisposition and some combination of a variety of stressors, which differ from one case to another, but include physical, chemical, biological, and/or psychological/emotional stressors. The retroviruses would fit under biological stressors in this model.
The genetic predisposition has not yet been completely defined, but there is evidence that suggests that there is a genetic predisposition from family and twin studies and from the few polymorphism frequency studies that have been published for ME/CFS.
I have reviewed the histories of a fairly large number of PWCs, and have also read the published "risk factor" studies, and I think this statement fits all the cases of which I'm aware. There is some complexity in the etiology, because every history is different. However, they have in common that stressors are involved, and the body's nonspecific stress response system ties into the biochemistry by lowering glutathione, and in a person who is genetically predisposed, I'm suggesting that that brings on a sequence of cause and effect that produces the vicious circle that keeps ME/CFS chronic.
The difficulty in treating ME/CFS is that one cannot recover simply by removing the stressors that contributed to the onset, though it is important to do that, because a vicious circle mechanism is set in motion, involving the methylation cycle, glutathione, and folate, and this vicious circle must be broken. But yes, there definitely is a cause and effect tree in the pathogenesis of ME/CFS.