Is chronic fatigue syndrome a connective tissue disorder? A cross-sectional study in adolescents (2005) [
10.1542/peds.2004-1515]
This study implicitly assumed connective tissue damage under
"connective tissue disorder" and bases their inconsistent conclusions based on this assumption. The hypermobility data has since been confirmed in the following study.
Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study (2021) [
10.7861/clinmed.2020-0743]
I'm not familiar with the different mobility scoring methods, but I assume this is the reason for the inconsistencies in that regard.
Regarding the pathology, I assume that the methylation/folate/choline/NAD recycling issues interrupt proper collagen synthesis and assembly.
For an understanding of the metabolic processes:
Amino acid management in cancer (2015) [
10.1016/j.semcdb.2015.08.002]
Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues (2017) [
10.1038/srep45913]
Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (2020) [
10.3892/mmr.2020.11339]
I picked the first two studies only because they elaborate on the link between amino acid methylation/folate/choline/NAD recycling and collagen synthesis. The third study finally explains how this all contributes to collagen-mediated pathology, but also how senescent cells affect this. The senescent cell model is consistent with the pathogen-mediated model that I assume happens in CFS/ME. They also elaborate on the protective role of estrogen, but this isn't the primary driver of the collagen issue. It might explain, however, why women are affected more frequently.
