Gene Identified In 28% Of Idiopathic Small Fiber Neuropathy

[davecom]

I hope this article wasn't already posted. 2012 from a team of mostly Dutch authors:

[PDF] from researchgate.netresearchgate.net [PDF]

Interestingly they refer to autonomic dysfunction amongst patients with the identified gene and suggest it maybe worth testing for in idiopathic small fiber neuropathy patients.

* I meant to write 28% of IDIOPATHIC Small Fiber Neuropathy.

[corina]

I edited your topic title Dave.

[HopeSprings]

Yup, I asked my POTS/neuropathy neurologist about this and he thinks it's a very promising area of research and may eventually help some of us.

[Suthrngal]

What's the gene? Wondering if it is identifiable on my 23amd me genetic test. Anyone?

[davecom]

Checkout the article; the gene is in there.

[Zap]

One of the major issues here is bridging the gap between identifying the root cause and treatment. 23andMe does have SCN9A or at least part of it in their raw data but I haven't found a matrix that indicates which alleles are mutations to interpret it yet. Might have to scour through all the SNPs and create a table, of sorts OR have the testing done to get a concise answer.

SCN10A is also potentially a source of issue here, which is Na(V)1.8 - and is also potentially responsible for some chronic pain and other neurological issues.

There has been work on creating Selective Sodium Channel Inhibitors - as currently most meds used for chronic pain are being used off label and are suspected to modulate sodium channel activity in addition to what their primary functions are. Hence why they may help with pain, but cause many other undesired side effects. This is a widely held suspicion about Tricyclics and why they work for pain.

I'm presently putting together a matrix for SCN9A and SCN10A to cross-check for mutations. I'll post back when I've managed to sift through everything. Guessing my neuro will at least try to order the tests to verify my work.

This is exciting, as I may have also found a few novel medications that might be just the thing for modulating these sodium channels with minimal side-effects.

[Zap]

Okay, that was a bit faster than I expected....

I found 27 SNPs in SCN9A and 5 in SCN10A in databases. Unfortunately, 23andMe doesn't have many of the SCN9A SNPs, so it may be advantageous to have the gene sequence performed. The ones that are present:

SNP / Typical Allele / Risk Allele / Disorder(s)

SCN9A

Rs41268673 / G / T / Primary Erythermalgia

Rs4438497 / T / C / Dental Caries

Rs6746030 / G / A / Nociceptor Excitability, Increased Pain, Primary Erythermalgia

SCN10A

Rs6795970 / G / A / Variation in Cardiac Conduction

Rs6798015 / T / C / Variation in Atrioventricular Conduction

Rs6800541 / T / C / PR Interval

Rs6801957 / C / T / QRS Duration, Cardiac Ventricular Conduction

These are all the ones I found that 23andMe has data for... I'm not 100% on the distribution of risk on the last SCN10A SNP. It appears that variation is more common than on the rest of the SNPs listed.

The present tests they were trying to cross-link in the study above were SFN diagnosed via biopsies and SFN diagnosed via QSART with sodium channel mutations.

[davecom]

Hey Zap,

Great work looking this stuff up and doing some research. The sodium channel blocker idea is actually mentioned in the original article. I have an initial appointment with a geneticist in about a week. I am going to bring this article with me now that I have the SFN diagnosed by biopsy and the suspicion that it is idiopathic.

Reading your past meds and diagnosis; seems like we might have something in common.

Let me know if you progress.

[Zap]

Okay, I've got my neurologist appointment this week. I'm going to be pressing with this research information in order to attempt a novel drug therapy.

The doctors can't have it both ways - if it is truly idiopathic, then research is showing sodium channel problems. That is grounds for attempted treatment with a drug that would possibly be indicated for POTS from many angles. At least from my research, which I know can be somewhat misleading as to real world efficacy, this would theoretically supplant common therapies like beta-blockers for a number of reasons, not limited to the fact that it doesn't cause BP drop.

At any rate, the biggest claim to fame is modulation of the NaV 1.7 and NaV 1.8 channels, those implicated in idiopathic small fiber neuropathy. Given the immense amount of pain I've been in lately, I'm certainly open to trying something to help. Unlike most other existent meds that are believed to modulate these sodium channels, there appears to be a LOT less side effects implicated from the data.

I'll post a follow up here again at the end of the week after my discussions at my appointment. Hopefully the test-run will be approved and we can see if there is any real world efficacy.

[davecom]

I saw a geneticist and showed her the article and she was receptive. I probably won't get testing back for 5 months though... Keep me posted on what happens with you.

[Zap]

Wow, all my appointments have been a total bust lately - I'm being sent to an Endocrinologist for abnormal acylcarnitite profile and based on my fasting causing remission of some symptoms.

There was too much concern over orthostatic issues (despite that my BP doesn't drop) to try my experimental treatment right this instant, though I asked for something to help control the migraines.

Given my GI test results (stomach emptying EARLY - seems incorrect due to my other GI issues, but could be possible) and esophageal transit delays / sphincter dysfunction I now have to see a GI specialist. The gastric dumping could account for a number of my autonomic symptoms.... but I've never had a bypass or anything, just lucky I guess to have this horrible problem in spite of that.

But maybe blood sugar flux could be causing the migraines and symptoms if fasting makes me a bit better.... seems like a few connections are converging for a change.

I wish I could get the testing to rule this problem in or out. Another article I found implicates low NE in some of these issues too. A few new things to explore, but still no reprieve from all the symptoms at this point.

[davecom]

Keep up the good fight. I'll post back here when I get the genetics results back in a few months (I've given blood... apparently it's just that sort of process).

[issie]

Zap,

Are you gluten free and dairy free. I know we have talked about this before. But, the more research I do on it - the more I'm convinced it plays a part in not only intestinal things but also autoimmune things. It can address mutations in the methylation pathways too. Since you are having issues with amino acids (proteins) maybe a different source of protein would be handled differently in your body. I'm listening to a vegan seminar that is all this weekend and have already listened to two days of it. I sent you the link. I can't post it here - as some of the people are advertising books and things they have written. But, it is convincing me even more what effects this may be having on us all.

I used to have IBS, and borderline sugar problems with it sometimes dropping low and other times being a little bit high. I don't have any problems with either now. Also,I make sure that I'm keeping glutamates out of my diet as that can also cause headaches and not to mention issues with nerves and moods.

As for NE ---some of us are really thinking that NE is very necessary and a compensatory thing. When you have this release - it causes this uncomfortable surge. But, that is probably the bodies way of getting blood back up to the heart and brain and a very necessary thing to have happen. I have high NE levels with standing. It causes all sorts of uneasiness and tachycardia - but, I'm not trying to block its affects. In fact, have done an experiment to increase it more and try to keep the levels up higher and more steady.(With the idea that if it is more level, it may prevent the surges.) It worked for a short while and then the med became ineffective, and unfortunately, it only lasted 2 days and on the 3rd day no longer was effective. I also couldn't continue taking it because it was hard on my kidneys. What is it? Sudafed. All I can figure for why it worked was maybe it helped the body to keep the levels more steady and the body didn't have to work as hard to produce it and release it in a surge fashion and things stayed more level. One other person that tried it ---was doing research to try to figure out why it helped ----but, I didn't hear his conclusions and it doesn't appear that he is participating on the forums any more.

You might also take a look into CO2 and NO - as this can also play a part in our dysfunction in addition to NE. I know there are many thinking that SFN is a big player here and I do think it plays a part ---but ultimately, I'm thinking that genetics pre-dispose us to certain things and something triggers an activation of those genes and then our autoimmune systems are faulty and that along with inflammation may be what causes us the most grief. Working on the immune system and inflammation may bring some really good results. (I'm encouraged with my results - so far!)

Issie

[Zap]

It is unfortunate that when this cascade of symptoms took most of my life away, I already was following a very strict vegan diet, without much grain of any type. The problem is no matter what I do that the issues tend to persist.

The funny thing is my NE testing was normal - both laying and standing. I thought for sure that it would be elevated, but it wasn't so. I tried the Sudafed, but it wasn't effective at all for me. Again, it was surprising. But I don't have the blood pressure disturbances that most do. My etiology is a bit bizarre, really.

I would ideally like to do the SFN genetic test. That would at least possibly determine whether that is a defining factor here. Even the turmeric seems to not be helping me as much as it used to, sadly.

I may be doing a juice fast again, so we'll have to see what I find. Speaking up about it (insanely) has now convinced the doctor that I'm allergic to something that is causing the migraines. Unfortunately, I'm now starting to think that it is more related to the possible dumping discovered in the gastric tests than any particular food, as I've never in all the elimination dieting I've done over the years been able to find a trigger for the migraines.

I've also discovered a doctor that believes in functional medicine and that many ranges for tests are inaccurate and too wide. I'm possibly thinking about having him evaluate any endocrine tests I run, as there could be a "mild" deficiency.

On that note, I think that most doctors consider anything not life threatening "mild" and blow it off. I'm sick of being dismissed when others on this forum have had WAY more attempts at finding a treatment to ameliorate even some of the symptoms and improve quality of life.

[issie]

Sounds like you need a break from the turmeric. We are supposed to do that anyway, as they will stop working after awhile. Maybe, taking a break and then starting back again later, will cause it to start back helping. I'm on a break from it and ginger right now - myself. I started a different herb to help with inflammation, pain and immune system. We will see how it goes.

I know how frustrating it gets. You wouldn't believe how many doctors I've been through to figure out what I have. And then how much research I've done to learn more and sometimes present it to doctors and then have them either confirm or be able to dismiss what I'm thinking. We do have to educate ourselves on so many functions of the body - in order to track down and figure out what is going on with us. You're getting closer. Even with every dead end we hit - that gives us an answer and we can go on to the next thing after that.

Issie

[davecom]

Zap,

According to your signature you have small fiber neuropathy? Then you probably already know the cause of your POTS and probably a lot of your other symptoms therefore. The question is, what caused your small fiber neuropathy.

I'm in the same boat

? -> Small Fiber Neuropathy -> POTS and other symptoms

I'm trying to fill in the question mark. The SCN9A gene is just part of the search.

Keep searching!

[issie]

Dave, My feelings on SFN is that is a symptom and not the core problem. I think we are predisposed to something with genetics and then the faulty immune system starts to attack things it should not and/or allows things to remain that it should attack. This in turn causes lots of inflammation. I have neuropathy that seems to have a genetic component (both dad and granddad) but, mine is getting much better since I've been working on my immune system. One other thing I've noticed is that it is worse when I have more pooling and therefore, more swelling/edema in my feet and legs. But, compression will also make it worse. Pressing on the nerves from an external source for sure causes me more numbness and pain.

Issie

[Zap]

Funny, that is, that I've not so far needed a break from the turmeric, but maybe I have finally gotten to the point where I do.

I've been theoretically diagnosed based on the fact that I have abnormal QSART, TST sweating response, and slightly diminished tactile test response in the feet. No biopsy so far, but it is fairly certain - my neuro says that it isn't worth the pain of the biopsy (which used to get ordered routinely in the past) as it doesn't change the course of action. I'd like the genetic tests as 23andMe isn't currently testing most SNPs.

I will definitely not stop the search, and I am still suspicious that my cause is inflammatory/immune as my response to steroids is pretty indicative. I am to see an Endocrinologist soon, and maybe we'll find HPA-axis malfunction, which could explain some of these things. The recent esophageal and gastric emptying tests show malfunction, which honestly backs up the SFN theory anyway.

ALSO, I discovered yesterday that the Benfotiamine I was taking was such a miniscule dose that it wasn't even on the charts for the survey being done for CFS based on the Italian study. Upped to taking 6!! capsules at a time and all of a sudden after I was taking just one, twice a day, for over a month, that it is finally doing something!! It gave me quite a bit more energy than I previously had. Just have to see whether it drops out or works long-term, but it looks promising. Felt a lot more like myself, for a change (especially as of late). Of interesting note, regular B1 didn't seem to have the same effects.

Still chasing the SFN issue, regardless, as it seems to be the closest thing to a cause I've found so far.

[issie]

I had done research on Benfotiamine and thought it would be more beneficial. Of course, I get a lot of B1 with my vegan diet. But, I do take benfotiamine a few times a week. I found that it upped my sympathetic system too much to take more. But, glad it's working for you.

http://forums.dinet.org/index.php?/topic/23769-b-1-what-could-diet-changes-accomplish/?hl=thiamine#entry222075

Yeah, I know about the stopping of herbs and figured out that maybe that was why it wasn't working for me either. Sometimes, we just need a reminder that we need to do the things we know about. LOL! I'll stay off for awhile and then go back on. Duh! Right?

With the SFN testing - sometimes it gets missed. They usually do two biopsies - but, I have heard of it being missed.

Issie