Chronic fatigue syndrome and autism

Townsend Letter for Doctors and Patients, Oct, 2006 by Richard A. Van Konynenburg

For the past ten years I have been studying chronic fatigue syndrome (CFS) as an independent researcher. Over the course of several years, I developed a hypothesis for the pathogenesis of this disorder that prominently featured the depletion of glutathione. I presented a paper on this hypothesis at the AACFS (now the International Association for Chronic Fatigue Syndrome) meeting in October 2004, in Madison, Wisconsin. (This paper can be found at http://www.cfsresearch.org/cfs/research/treatment/15.htm.)

Anecdotal experience of people with CFS who acted upon my hypothesis suggested that while some were able to raise their glutathione levels by various means and experienced benefit from doing so, others were not able to do so. At the time I wrote my poster paper, I was aware of these anecdotal outcomes, and I acknowledged in the conclusions of the paper that there appeared to be factors blocking the raising of glutathione in CFS. At that time, I was not sure specifically what those factors might be. I also knew that there was evidence for a genetic predisposition in CFS, but I did not know the details of the genetic variations involved.

Shortly thereafter, I became aware of the work of S. Jill James et al. in autism (American Journal of Clinical Nutrition. 2004 Dec; 80(6):1611-7). The authors of that study found that glutathione was also depleted in autistic children, that this depletion was associated with a partial block in the methylation cycle (also called the methionine cycle), that this partial block was associated with genetic variations in the genes for certain enzymes and other proteins associated with the sulfur metabolism, and that it interfered with the synthesis of glutathione. The authors also found that by using certain supplements (methylcobalamin, folinic acid, and trimethylglycine), they could lift the block in the methylation cycle and restore the glutathione level.

Upon learning of this work, I became very interested in possible parallels between chronic fatigue syndrome and autism. I attended the conference of the Defeat Autism Now! (DAN!) project in Long Beach, California in October 2005, sponsored by the Autism Research Institute, headed by Dr. Bernard Rimland. As a result, I became convinced that the genetic predisposition found in autism must be the same or similar to that in a major subset of CFS, and that the resulting biochemical abnormalities were also the same or similar. As far as I know, the genetic variations in people with CFS have not yet been studied in detail or published, but I am optimistic that this will occur soon because of the rapid advances in the technology for doing so and the current active interest of at least three groups in the US and the UK in genomic aspects of CFS.

There are obviously major differences between CFS and autism. I believe that these differences result primarily from the different ages of onset. Autistic children experience onset early in life, before their brains are fully developed. I believe that this gives rise to the very different brain-related symptoms seen in autistic children from those seen in adults with CFS. However, many similarities exist in the biochemistry and symptoms of these two disorders as well, including oxidative stress, buildup of toxins, immune response shift to Th2, and gut problems, for example.

The triggering factors for autism and chronic fatigue syndrome are also largely different. Although this subject remains controversial, there appears to be substantial evidence that vaccinations (containing either a mercury-based preservative or live viruses, many given within a short period of time) were responsible for triggering many of the cases of autism in genetically susceptible children (D. Geier and M.R. Geier. International Journal of Toxicology. 2004 Nov-Dec; 23(6):369-76; and A.J. Wakefield, several publications beginning in 1997). In CFS, a variety of triggering factors (physical, chemical, biological, or psychological/emotional) have been found to be involved in various cases, as reviewed in my poster paper, cited above. All these factors have a demand on glutathione in common.

It appears that genetically susceptible persons are unable to maintain normal glutathione levels when the total demand is high, and that once glutathione drops sufficiently in a genetically susceptible person, the sulfur metabolism becomes disrupted. In many cases, the methylation cycle (part of the sulfur metabolism) becomes partially blocked, and the result can be a depletion of some or all of several important sulfur-containing metabolites, including S-adeno-sylmethionine (SAMe), cysteine, glutathione, taurine, and sulfate. A vicious circle is thus formed, and the depletion in these metabolites causes an avalanche of pathogenesis, since they all perform important functions in the body. I think that much of this pathogenesis is common between autism and CFS. In autism, the loss of methylation capacity because of the drop in SAMe appears to be responsible for much of the interference with normal brain development.