I tried to post this to the Ehlers-Danlos subreddit so that other people could be helped, but unfortunately, the mods there wont allow it. I'll post it here, and perhaps it will make it to those who need to see it and whom it could help. Basically, how I partially reversed my fiancé's EDS.

So introduction, I'm a Family Doctor and HIV specialist, and my practice tends to cater to the LGBTQ population. Many years ago, I noticed a correlation between gender dysphoria and POTS/MCAS/Hypermobility/Hashiomotos/IBD or IBS/Autism/ADHD/Myopia and a few other linked things that all exist at a common genetic locus (Chromosome 6p21). My research team has a pretty good theory as to what's going on with that, and we call it Meyer-Powers syndrome. But I'm not here to talk about that, I just wanted to give the context that I'm a doctor who has about 1000 patients with Hypermobility/EDS I have access to the mayo genetic testing for it right out of my clinic which has been handy. I've had to "gitgud" at treating EDS, as nearly 1/3 of my patients meet beighton criteria and that's a lot of bendy people. Dealing with hypermobility is like almost 10% of the complaints at my practice.

Ironically, My fiancé is a 33 year old young woman with hypermobility. She's tiny, 5'4" about 100 lbs, and has always been thin. She complained of chronic joint pain a lot, and when I touch her arm or leg, her skin moves more than it "should". Physically, she looks normal if you passed her on the street, but she has something going on under the hood.

I got the Mayo sequencing done on her first, and later, a 100x whole genome sequence, which both found she had a heterozygous frameshift mutation in FKBP14 which resulted in a stop codon gain. Effectively, 50% of her ability to make FKBP14 (the enzyme) produced by FKBP14 (the gene) is shot. She also has a mutation in FKBP22 but its unclear what impact that one has. REVEL score is high but there's almost no data out there on it.

This type of EDS is known as Kyphoscoliotic EDS, and is quite debilitating when homozygous. However, everything I read said that someone who was "a carrier" aka someone who only had one bad copy of FKBP14 should be basically asymptomatic and fine.

She's not fine, she has issues. I wondered why.

Review of her whole genomic sequence revealed homozygous C677T and heterozygous A1298C mutations of MTHFR (short explanation, the enzyme that turns folic acid into methylated folic acid for the usage of energy generation / NAD synthesis had some loss of function mutations.

For people with these MTHFR defects, you can simply give them pre-methylated folic acid and it sort of solves the assembly line problem. As a result, her NAD synthesis goes up, which in turn reduces oxidative stress.

As a result her weakened FKBP14 does not have to work as hard in the endoplasmic reticulum.

FKBP14 shares some protein folding domain with other FKBP proteins (other prolyl isomerases) in the ER. Certain ones, such as FKBP22, can be effected positively by various supplements, one of which is TUDCA. I started her on this as well, such that the enzymes sharing tasks with FKBP14 could take some of the load off of the weakened enzyme on those substrates where their Venn diagrams sort of overlap.

Imagine you have two finals tomorrow, one in calculus and one in genetics. You haven't studied, and so you're going to pull an all nighter. You have to split your time between the two things, and in all likelihood you'll fail. But if you had a twin sibling who was a calculus expert, they could show up and take the calc final such that you can spend all night focused on the genetics test. While this would be really morally wrong in real life, when it comes to cells doing such a thing, I think they can get a pass if it makes your EDS not as severe.

FKBP14 is involved in the folding of Type 1 and 3 collagen. (also 5) Vitamin C is a cofactor for the hydroxylation of Type 1 and 3 collagen as well, so I have her on 1g three times daily.

There's more that we do in her care plan, NAC, m-tor inhibitors, etc., but I'm not going to go and detail out the entire plan as that plan is hyper specific to her unique situation and that's not the point of this post. Your "supplement blend" will be different from hers unless you had the EXACT same genetic anomaly.

That being said, I always hear that "there is no treatment for EDS" and that's just not true. I cannot fix her broken FKBP14 frameshift mutation (yet). But I can support her weakened enzyme as much as I possibly can by taking load off of it by boosting other enzymes that share its targets, increasing the amount of energy available to her cells, reducing oxidative damage and ER stress, etc. etc.

In doing so, I can get the full 50% output from her remaining FKBP14. I can make it easier for proteins to fold in her ER in general, I can reduce her oxidative stress load which further enhances things.

Regardless, we started this experiment now over a year ago, and she is in considerably less daily pain, and can no longer touch her thumb to her wrist. Don't get me wrong, she's not "cured" by any means, but this has significantly blunted the severity of her disorder, as instead of having her diagnosis be "wibbly wobbly person with some sort of hypermobility syndrome", the answer is a highly specific FKBP14 het knockout and FKBP22 mutation of undetermined significance which I then was able to tailor some biochemistry mods and a supplement plan that caused considerable improvement. Its actually kind of wild, she looks somewhat younger as well.

Please do not take from this that I am advising these supplements for literally anyone

This ONLY worked for my fiancé as I knew EXACTLY what was broken, and did anything I could to learn how I could boost, support, or remove the workload of this crippled enzyme. Your EDS may be something 100% different from this, and you would only know if you ended up getting genetic testing to know specifically what's wrong. If you do find out, ChatGPT has been amazing for probing around what I could potentially do to help these genetic problems, or support whatever weak enzyme it is that any other patient I have is suffering with.

I hope this is useful to you all, and that perhaps if you are lucky enough to have whole genomic sequencing available to you, that you can use it like I did for my partner to help her with her condition. Even though I can't "fix" it, she is a lot happier, less bendy, and in far less pain than she was, and I'm really grateful for that.