More expert help with genetics
 

Hi,

Just to update you, my sister and I are getting ready for our appointment at Oxford UK to see another professor in SFN who deals with genetics. We are there for 2 days while we have a number of blood tests looking for variants and full blood screen again. We have had SCN9a & 10 already which came back negative.


My biopsy showed an increase in nerve fibers, whereas my sister's showed a loss of nerve fibers but did show that fibers were re-generating.

I've today seen my local neurologist who feels this is genetic. My sister and I have no family history of SFN. This started for both of us within months of each other in December 2012. However, my 5 year old son has had complaints of bugs crawling all over him and feeling itchy. I am still trying to understand the genetics, as I thought genetic SFN would be passed to a child in an autosomal dominant inheritance. My father or mother have never had any complaints of SFN, nor my grandparents or great aunts and uncles or aunts or uncles. Its just me and my sister, so im presuming it can't be a sporadic thing as we both wouldn't have it.

Professor i spoke to said it could have been a virus, or autoimmune. Its so confusing, as one says yes it must be genetic if sister has it, then the other says well its not in keeping with genetic channelopathies as you don't get increased fibers with that. He then went on to suggest is in keeping with autoimmune, which IVIG has been suggested.

Does anybody have any clue. Hoping i can come back from Oxford with some answers!

Lou Lou

Were you tested for the MTHFR methylation errors -- this is a DNA test. ?

I don't think so, what is this test for?

Autosomal dominant diseases arise when somebody has inherited a mutant form of a gene which codes for a protein which has a pathological "gain of function" effect.

They are very rare and show a very strong genetic pattern. If your SFN arises from an autosomal dominant effect then one of your parents would also have SFN as would one of their parents and so on. The fact that this is not part of your family history means that an autosomal dominant effect can be confidently ruled out.

The MTHFR gene effects which mrsD has mentioned are different. Mutants of this gene (there are a couple of common ones) lead to its encoded protein having an impaired function. This can have many effects and is certainly worth checking out - the Oxford geneticist should be able to advise you about this.

Thanks Kiwi. I also wonder if members of my family did have this they had it mildly so didnt say. My dad died at 57 of pancreatic cancer. His wife my step mum said he never had sfn complaints. My mum is obese and is in pain from weight but not aware of any complaints re sfn. Spoke to my 88 year old grandad who says never heard of this type of complaint in family. Dad who died had twin brother who had no complaints. Don't understand how this can be genetic. With the gene Mrs d mentioned, would I not have a vitamin deficiency? All my blooks show normal?

Methylation errors prevent nerve repair and maintenance.

B12 and folate have to be methylated in the body, to work in the tissues. If this fails partially or completely the body cannot function properly.

It is turning out to be more common than once thought (up to 40% now), and some
people posting here are finding they have some degree of mutation when they end up here. Most doctors still do not investigate this, even though it has been a decade or so since it was discovered.

The methylated form of B12 is called methylcobalamin. The methylated form of folic acid is called methylfolate. If one has one of the methylation mutations, these supplements can be taken to correct the lack and restore normal functions.

Here is a link to the information about it:
MTHFR Mutation | MTHFR Gene Mutation | What is MTHFR? - MTHFR.net

Your B12 level should be at least 400pg/ml.. Labs are still using the old values that start at 180. If you are calling you labs normal, look closely to see if you are being compared using the old outdated range.

Thanks Mrs D i will look into this.

I am wondering if anybody in my family has had this before but not mentioned anything as wasn't bothersome, i would have thought if it is genetic like my local neurologist has suggested it is, would fall in an autosomal dominant pattern. Kiwi suggested this can't be the case as there would be a strong family history. It is confusing, as the Dr's say one thing but it doesn't make sense when you look at it. I am worried for my 5 year old son who has complaints of SFN.

When I started reading about MTHFR it was just over a decade ago. Back then I recall the Merck paper, saying about 10% of adults have this.That has changed over the years to now about 40%.

However the DNA test shows other things too. Janieg here found she had an error processing biotin (a B-vitamin). This is not common, but she also learned that babies born now get tested for this at birth. She is missing only one gene and so has avoided major symptoms until now. If people are missing both genes however, the symptoms are severe and present at birth. These babies have obvious weak muscles and other problems.
Charcot Marie Tooth (CMT), a genetic form of PN, is complex and has many variants too. It can present in childhood.

The biotin problem is treated with biotin in high dose daily. But as of yet the CMT does not have a treatment designated for it.

Not all genetic problems have been identified yet, but certainly we do have a handle on some of them.

This is a bit complicated but mutations in the MTHFR gene are not autosomal dominant. The full name of the MTHFR protein (coded for by the MTHFR gene) is methylene tetrahydrofolate reductase. It is an enzyme which, among other things, has a role in methylation of Vitamin B12 and folate to give their active forms.

The most common mutations in the MTHFR gene are C677T and A1298C. These are called Single Nucleotide Polymorphisms (SNPs) and their effect is to change the sequence of amino acids (one change for each mutation) in the MTHFR enzyme, leading to a decrease in its activity.

Everybody inherits two copies of the MTHFR gene, one from each parent.

Scenario 1: If both copies of the MTHFR gene have C at position 677 and A at position 1298 then the encoded MTHFR enzyme will have high activity. All other combinations can and do happen.

Scenario 2: One copy of the MTHFR gene might have T at position 677 and A at position 1298 and the other copy might have C at position 677 and A at position 1298. This will lead to slightly reduced levels of fully active MTHFR enzyme.

Scenario 3: Both inherited copies might have T at position 677 and C at position 1298. In this case the activity of the encoded MTHFR enzyme will be very low.

All of the other scenarios are somewhere between Scenario 1 and Scenario 3.

I am trying to remember, did you and your sister live in the same place or visit with each other very frequently when the sfn came on?

[QUOTE=Healthgirl;1241615]I am trying to remember, did you and your sister live in the same place or visit with each other very frequently when the sfn came on?[/QUOTE

Hi Healthgirl. My sister spent a lot of time at my house at the time of onset. It stared in both of us in December 2012. It was within weeks of each other as we were both seeing neuros that thought we were mad. The fact we were both seeing one at the same time they found quite unbelievable. Sister sent to see a shrink. I was sent to see someone about health anxiety! I told the neuro this and his reply was well others in family would be affected like husband and then said because me and my sister both have inflammation of nerves it must be genetic. I said well proff I saw in London said ours wasn't a channelopathy . He said don't take too much notice of that and said see what prof says in Oxford. He can check for other genetics. I'm going to ask them about the one Kiwi and Mrs D mentioned .if the specialists in Oxford can't give me any answers I'm at the end of the road.

I think we are very similar!
Hopkins thinks I have an scn9a mutation causing SFN.
I did 23&me and did find a mutation
That can cause increased pain by affecting sodium channels.
My symptoms are bilateral frontal thigh burning sensations and
My toes can burn and turn red if I exercise in the evening in sneakers or before bed. I think it may be caused by erythromelagia or SFN.
Biopsy was done twice 18 mo apart. Most recent test shows my ankle at 29fibers/mm when abnormal is 5.
I have noted that fibers are increased from before by about 50%!
My levels appear to be slightly above normal range
My mom complains of her legs feeling heavy that she related to a mini stroke.
My dad has Parkinson's and my younger sister developed MS ( first cousin too)
A year before my symptoms started.
Any thoughts for me?

[QUOTE=LouLou1978;1241628]Dear loulou,hope u will find some answers,,**

Could there be mold in either location you and your sister spent a lot of time together in 2012? Just curious. Not sure what to think of that theory, but we did find mold in our old house when we were moving and had to get rid of the furniture. I didn't think a whole lot of it then, but it's the only thing I can say I know we were exposed to. Also did you have any renovating going on in either location? Sheetrock dust, solvents, paint fumes, floor refinishing, etc? We also had that going on, so I honk one of the two are linked to putting the genetic switch into overdrive for us. What else does your son say?


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I don't think we have any mold but we were having our bathroom refurbished at time of onset.

My son had mentioned crawling and that his underwear feels painful. The proff, has said not to read to much into this at this point in time. We have to wait 3 months for results from sodium channel mutations. Did you ever have these tests Healthgirl?

My symptoms are slightly different. I have had Scn9a & 10 but they came back negative. However, the university who have done further genetic testing are saying that there can be variants of these, so they are checking them again. I won't get any results for 3 months. They said the chances of them finding a mutation were about 20%.

I don't have any redness with pain, it does sound a bit like erythromelagia but i'm no expert on here. This is just from what i have read. I know there will be a sodium channel blocker which blocks the scn9a - naV 1.7. This will be out in about 5 years according to the Professor.

How old is your son?

He is only 5. My other son seems o.k who is 9. The proff said you can have the mutation but it doesn't always lead to symptoms so this is why there is no past family history.

Did you have symptoms as a child?

When I look back, I had mild dysautonomia, heat intolerance, joints that would crack out and back in, but was pretty much a normal kid and it probably all could have fallen under an anemia diagnosis since I was anemic. Later in my early twenties, my SI joints would go in and out and cause some problems here and there and I became hypoglycemic, but controlled it with protein every 2.5 hrs and was fine, Thirties I felt better than I ever did, knew how to take care of my idiosyncrasies and had 3 kids by then. Two of my three had some of my "sensitivities", but the other had none. I can tell you that never in in my childhood or whole life until I got sfn, did I or my kids have nerve pain, crawling, numbness, or tingling. So I am having a very hard time accepting that a mutation is the answer to this. Obviously we were genetically predisposed to what ever happened, but life was pretty normal before this. Maybe I'm just in denial.

Hi Healthgirl - No i never had problems as a child. We were always quite well. Our situation was similar to yours, we all got symptoms about the same time. I mean, within weeks of each other. I asked the prof. and he shrugged his shoulders and didn't think it was connected. Healthgirl, do they they think you have EDS?

Yes, that was the conclusion reached by my new young neurologist. She had all the assorted files on my case and had two children (med students) ask questions about the me and the kids, as did the genetics department who had no solid answer as to why we could all be affected so severely in the same time frame. There answer was "something heritable/connective tissue realm/ nervous system and then sent me to rheumatology. Rheumatology sends me to neurology. They send me back and fourth to each other. They all scratch their heads and say it must be autoimmune on top of EDS, but no one wants to keep trying to figure this mess out or try treatments.

Frustrating, isn't it? With my latest dive into the biotinidase thing, this pediatrician in Detroit who spoke with me even seemed thoroughly disgusted that my internist didn't event ATTEMPT to learn anything to help me interpret my results. You'd think just out of curiosity, if not out of a sense of duty to her patient, she might have at least tried. Nada.

I've debated trying to get in to see a metabolic specialist at Hopkins, but I'm so disgusted with mainstream medicine right now that I could scream.

Hi janieg & Healthgirl

Just to add something, which may be slightly irrelevant, to your EDS discussion, (Ehlers-Danlos Syndrome). I recently watched an episode of the TV series "Code Black" where a young woman was diagnosed with EDS in the ER - by chance - supposedly difficult to diagnose.

Unfortunately I've deleted it already from my recorder but I'm fairly sure it was Series 2 episode 10 - you may be able to find it online. Given that it's a TV show with heaps of 'artistic license' there may not be too much useful info in there for you.

All the best for finding something that helps you to manage the condition.