I have many symptoms of sensory SFN - but haven't been officially diagnosed with it by the neuros I've seen.

I also recently found out that I have significant methylation profile issues. (I am homozygous for 4 gene mutations including the A1298C gene, and heterozygous for 8 other mutations. However, I am "normal" on the C677T gene.)

There's been a fair amount of discussion here about methylation issues and MTHFR mutations - but has anyone here really linked their neuropathy (particularly SFN) to their methylation issues?? And, have they seen any improvement in their neuropathy through supplementation to address the methylation issues??

It would be difficult to say if the methylation issues CAUSE PN.....
But they for sure will affect healing. So that small damages to nerves and other tissues will accumulate over time, and not be repaired.

Poor methylation results in elevated homocysteine, and this does do damage thru inflammation to blood vessel interiors. (called endothelial lining).

http://doccarnahan.blogspot.com/2013...-big-deal.html

Research into this area is just beginning. I think with time more
detail will emerge with various illnesses.

I still haven't found that helpful diagram someone posted at one point, but I did find this link to a helpful document that provides some concise information.

http://www.vsan.org/rok-az/methylati...ry_sheet_1.pdf

That is a pretty good rundown....but Dr. Yasko concentrates on Autism, so she does not list other conditions commonly affected by these mutations. She is only interested in those affecting autistic behavior, etc.

Thanks janieg, based on the link you sent, I have the following status and issues:

CBS C699T (+/+) = homozygous defect. Both genes affected. Significant propensity for ammonia detoxification issue. Will need to be careful with sulfur containing supplements, ie. MSM and medications, ie. DMP

COMT V158M (+/-) = heterozygous. Partial defect in system = partial ability to use up CH3 groups. Will be able to handle some methylating supplements, ie. Methyl-12, SAMe, Theanine, DMG.

MTHFr C667T (-/-) = no mutation – enzyme works efficiently to convert homocysteine to methionine.

MTHFr A1298C (+/+) = homozygous mutation. Both genes affected. The enzymes system works very sluggishly which significantly impairs the conversion of BH2 to BH4 and its related effects.

MTR A2756G (+/-) = heterozygous mutation. Partial defect in system. This defect causes an INCREASE in enzyme function which increases the risk for methylation or methyl group depletion. Will be better able at handling a variety of methylating substances such as Methyl-B12, DMG, Theanine, SAMe, etc.
VDR Bsm/Taq (+/+) = homozygous mutation. Both genes affected. If mutation is present will be more sensitive to methyl donor supplements, ie. Methyl-B12, SAMe, DMAE, Theanine, DMG, TMG. Also, will need to watch for behavior issues related to fluctuations in dopamine production – mood swings!

So, with the A1298C mutation, there isn't the major issue with homocysteine. There's more of an issue with lack of BH4. And, some of the other issues seem to cancel each other out (one causing sensitivity to methyl donors, the others not, etc.) In addition, there's another half dozen mutations - so it all gets very confusing. I'm beginning to get some ideas on where to start, and will let you know how things come along.

Also, starting to search for an integrative medicine doctor in my area that has experience with treating complex methylation issues. Yeah I know - good luck with that, right ??

In case you haven't already checked this site, you may find someone in your neck of the woods. Also consider using one not in your area who will do phone consults.

http://mthfr.net/mthfr-resources/

I was just going to post the link Marlene posted.

I can't decide if it's surprising or not, but there's not a single doctor on that list from Maryland.

Ragtop, what is your FUT2 status? It affects the gut, B12 levels, etc...

If you don't know how to search for specific SNPs, use the search feature on the SNP ID (rsxxxxx), then just click on the results in the SNPs section.

FUT2 rs492602 G GG +/+ +/+
FUT2 rs601338 A AA +/+ +/+
FUT2 rs602662 A AA +/+ +/+

Or cheating, here are the links that will show your status. You just need to login.

https://www.23andme.com/you/explorer..._name=rs492602
https://www.23andme.com/you/explorer..._name=rs601338
https://www.23andme.com/you/explorer..._name=rs602662

I'm homozygous across the board...a non-secretor.

Looks like I'm the opposite of you on these Genes:

FUT2 rs492602 AA
FUT2 rs601338 GG
FUT2 rs602662 GG

I assume you meant that you are homozygous for the mutation - which means I'm "normal" on these?

Thanks marlene. Looks like there are a couple in my area I can call.

Yes, you're normal...a secretor. You secrete your blood antigens into your bodily fluids. I don't. It alters body chemistry in ways they're still understanding. The one positive thing is that I can't contract a norovirus.

I asked because it affects B12 levels.