I have been puzzling over this lately. What are the possible causes of a partial methylation cycle block? Genetics is supposed to be one, but what if you don't necessarily have the genetics for it? For example, I have only one MTHFR SNP out of a possible four. My naturopath thought that was iffy as to whether I had a block. Then when I got the Vitamin Diagnostics Panel, I definitely had a block and a classic CFS pattern. And back when people were doing the DNA test their results were all over the place and didn't seem like genetics predicted anything except the CBS/sulfur?? thing. It's been awhile, can't totally remember. I know you mentioned Judy M and Jill James are looking at whether XMRV causes this. And I also found an interesting interview with Martin Pall which seems applicable: http://www.chronicfatiguetreatments.com/wordpress/treatments/interview-with-dr-martin-pall/ I think he's saying that a short term stressor would cause a short term problem with the methylation cycle. It doesn't make any sense to me that a short term stressor would cause a chronic problem, otherwise everyone would get a cold, for example, then be sick forever. Therefore, it also sounds like you would need a chronic stressor to create a chronic problem. In the absence of an obvious chronic stressor, then you're left with things like food sensitivities, toxic mold exposure, Lyme, or XMRV. Comments?