Small fiber neuropathy
 

Hi,

My first message here.
I'm 36 y.o, male. vegetarian for the last 5 years,
I first started my neurological diagnosis path 23 years ago, when i was about 13 y.o. I started complaining that my muscles start to burn when i do something continuous like using a spoon to eat a soup or holding a glass to drink water, this affects all my muscles.
CPK levels were at about 300, and muscle biopsy was taken - there was no evidence for muscular disease. Lactate and Ammonia blood tests were taken also while doing exercise and these were normal also.In the following years these symptoms continued. Couple years later on I started to feel 'waves' through my legs and through my hands. It came and it vanished after a period of time. There were also attacks of itching all over my body when exposed to heat. it vanished also. Then there was one time I went to the gym after a year I wasnt there, I exercised too intense for a first time and the next day i could barely do anything, muscles throughout the body were painful. I had rhabdomyolisis with cpk levels at 25,000. It went away after a week with fluids. A second muscle biopsy was taken and again was normal. cpt tests were normal also.
The waves continued. it appeared and disappeared. there were also times where some parts of the skin felt differently - sensitive to touch, burning but it went away after couple of days.
Then came the heat intolerance, I couldnt sleep when i felt it was too hot, I felt like my whole body is on fire. If i used the A/C things were better. 15 years ago my feet started to burn when it touched the ground, as soon as i lift them up it felt great., emg was normal. I think it came and vanished, or the pain degree changed.
There were time i felt i lost my balance, even if i sat on a chair.
Heartburn attacks for weeks, regardless of food.
The last two-three years, my palms started to get very cold when exposed to cold weather. color didnt change so it wasnt rynaud. sometimes the palms got swollen and painful, but it went away after several days. now the cold hands are almost constant.
Rheumatologic diagnosis was all OK, except for positive RNP, but ANA was negative, so they said its not that.
A year or more ago I started to feel strange when i used my mobile phone's touch screen to write messages, the screen felt different. Now it really hurts to tick the screen, the tips really hurt.
It seems like i lost the temperature and the 'real touch sense' in my palms and feet fingertips.
I'm also having bowel issues in the last months - lots of gas, in the mornings i can even go 4-5 times to the restrooms. I can see undigested food in the stool.
stool tests showed blastocystis hominis. Took flagyl antibiotics for a week, but the parasite is still there.

I had a skin punch biopsy to try and diagnose a small skin colored papules on the dorsal and dorsum. They couldnt identify what it is but one of the findings was: dermis changes including mild pre vascular inflammation changes - fibrosis.

I'm supposed to have genetic tests in 10 days for sodium channel mutation.

I'm looking for your help in trying to find the cause for this thing, what tests should i ask my doctors to conduct, what is the best center in the world to try and diagnose and treat this thing. any help is appreciated.

Wanted to add tests iv'e done:
Several EMG tests - all normal.
Two muscle biopsies - normal.
Brain MRA - normal.
Thyroid normal tests.
Autoimmune blood tests - all normal except RNP, but ANA was negative.
Fabry - negative.
Malignant hyperthermia - negative.

Hi madmax,

Sorry you find yourself here, but you have a lot of company.

Many of us are idiopathic and have no clue why we have neuropathy despite extensive work-ups. I'm currently exploring any possible genetic cause having taken an whole exome test. I'm on my own doing this, though. I have to sift through my results.

Are you here in the U.S.? The one thing I've not done is had a full-blown Lyme Disease work-up. At least one person here discovered the source of her problems doing that. I have a local Lyme Literate Doctor (LLD), but he doesn't take insurance, and it's $800 for the first appointment. That doesn't include any testing.

Janie

Hi Janie
 

Thanks for your reply.
I'm from Israel. Money is not an issue right now, and I also have an insurance.
Before we had our second pregnancy we did some gene testing and they found a mutation in IKBKAP gene IVS20DS.
Another genetic thing I'm trying to explore are those papules I have on my palms and feet, which I think are Acrokeratosis veruciformis which involves ATP2A2 gene.

I think I also see petechiae on my skin.

Any idea about these?

I have started today to take some supplements: B complex, Alpha lipoic acid and probiotics.

Did another run of blood tests yesterday, RNP is again high - 2.2(prev was 1.5), ANA pattern and titer are still WIP, i really pray it will return negative as last time.

I should see another neurologist in 10 days.

Hi madmax80

The IVS20DS variant of IKBKAP is relatively common in people of Ashkenazi Jewish background and can lead to sensory neuropathy. The "Molecular Genetics" section here might help you in discussing this with your health care team OMIM Entry

- * 63722 - INHIBITOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B CELLS, KINASE COMPLEX-ASSOCIATED PROTEIN; IKBKAP.

Acrokeratosis verruciformis is an autosomal dominant condition associated with mutations in the ATP2A2 gene. What that means is that it has a strong family genetic history - if one of your parents (and either of their parents, etc) has it then there is a 50:50 chance that you will.

The information here might help you in this context Acrokeratosis Verruciformis of Hopf: Background, Pathophysiology, Epidemiology.

Thanks kiwi.
I am Ashkenazi Jewish. But as far as I'm aware the xymptoms of familial dysautonomia are much more severe comparing to what I feel.

As to acrokeratosis - it seems like my father and sister have the same papules on their feet dorsal, but they dont have any neurological symptoms at all.

Did you look up those genetic results?

It appears to me that you have various risks for several diseases, which are all rare. (including dysautomnia, and malabsorption of fats because of pancreatic failure, and nervous tissue problems).

It might be best to see a good genetic specialist to find out which nutrients would be best for you. For example, if you cannot absorb fats from the diet well, you may need Vit A and E supplements.

Genetics is still an infant science, but you need to find out more about yourself. Getting MTHFR DNA test may show you have methylation failures and you may need methylcobalamin and methylfolate to correct that.

Genetic errors manifest differently in different people.

Not all cells share the mutation equally.

I have a friend with a daughter who was diagnosed with Turner's syndrome. When she went to a specialist, this doctor tested cells all over the girl's body and found only about 50% of her body was missing the X chromosome.

But this illustrates that the expression of DNA mutations are variable. One cannot take them literally. This is why having a specialist is a good idea to formulate answers or treatments.
Sometimes environmental stressors (illness/infections, excessive exercise, etc) may trigger symptoms.

Thanks mrsD.
I did see a genetics specialist something like 3 years ago. He sent me to do the brain MRA which returned normal.
Who is the best genetics doctor you know or best center i can try and reach?
I should have a full genetics panel next week where they will try to search for a sodium channel mutation.

You can search just as well as I can. I have no idea what is in the area you live in. However your heritage where you are suggests to me there must be genetic specialists where you live.

Ask to see what is in the test you are getting. Will it be a full genetic screen? Or only a partial for neuropathy? I think you should get a full test like janieg got for her issues.

Some doctors only test for specific problems and do not give a full workup. Did you check out her new thread yet?

It is sometimes difficult to shift from patient to being your own advocate. With time you'll learn much more if you are less passive with the doctors and do some research on your own.
Also make sure you get your B12 tested to see if that is seriously low. No supplements for several days before the test.

But for now, try not to overdo physical exercise, and eat a varied diet, avoid too much sugar and carbs. Look up each coded mutation and see how it impacts your metabolism. I found alot in just a few minutes. The malabsorption error you have suggests what nutrients you should concentrate on.
I would avoid the lipoic acid supplement as it takes up the multivitamin transporter, and prevents other crucial nutrients from getting to your tissues.

All you can do in the end is support your tissues with non-stressful activity, good food, good rest.

Madmax80, I have been thinking a bit about your genetic issues.

As far as your familial dysautonomia is concerned, this, coupled with the fact that genetic testing has shown that you have the IVS20DS genotype means that both your copies of the IKBKAP gene (on chromosome 9) have this mutant form of the gene. This is because familial dysautonomia has what is called an autosomal recessive pattern.

I do not know if your wife has had similar testing for the IVS20DS genotype but if she has it, (in the absence of frank symptoms), that means it is found on only one of her copies of chromosome 9. If so, that means that all of your children have a 50% chance of developing familial dysautonomia.

Acrokeratosis verruciformis is very rare and is not correlated with people from any given ethnic background. You could get tested for mutations in the ATP2A2 gene if you want to.

I appreciate that there are many hard concepts in genetics and molecular cell biology here. If you and your wife are not very familiar with these hard concepts then it might be an idea if you saw a professionally-trained genetic counsellor.

S/he should be able to talk you both through the implications of your genetics in ways that you can both understand.

Answers
 

Thanks mrsD.
I should be doing an Exome sequencing. Is this the right direction to try and find everything?

Because of the diarrhea i have been having for the lat several months i have started today a hipo-allergenic diet based on brown rice, vegetables and fruits. I also need to treat the blastocystis hominis parasite i have in my stool using antibiotics, hopefully to start next week after more stool tests.
My blood B12 levels are at 525 pmo/L after 2 days i didnt take my supplement.
I currently take a B-Complex, Alpha lipoic acid 600mg(should go to 1200mg in couple days, and a week after go to 1800mg daily) and probiotics.

Until last week when I met my neurologist and he let me know it's likely a small fiber neuropathy, I used to go to the gym 3-4 times a week, I'm running, I play professional table tennis. Now i'm afraid, although I dont think I should be.
I'm also having tiny fasiculations all over the last couple of days. I used to have those in the past, usually one area at a time and then it will go. I guess from the current stress i'm having, this is all over.

I have read that Phosphatidylserine might help with IKBKAP gene mutation symptoms. I'll consult with my doctor.

Answers
 

Thanks kiwi for thinking about the data i provided.

I do not have familial dysautonmia, just to be clear. just the mutation in the gene. My wife doesnt have this mutation, so we should be safe.

The acrokeratosis verruciformis diagnosis is mine and not the doctor's, yet. This is my assumption due to the fact i see those papules on my father's and sister's dorsals also. I should see a dermatologist with genetic diseases interest by the end of the month.

I also have a posetive rnp (1.7) and negative ana and have idiopathic small fiber neuropathy. So far it is the only abnormal tesr result i have. Dr.s dismiss it but i can't help but wonder if it has something to do with my neuropathy being it's the only abnormal marker.

Elevated RNP levels can indicate a range of connective tissue diseases but it does not seem to be associated with neuropathy. Generally a RNP test is not useful in people without elevated ANA (antinuclear antibody) levels.

There is more on this here RNP - Clinical: RNP Antibodies, IgG, Serum.

Exactly. I'm hoping mine will be negative as well.

Hi, Have you seen the private message I sent you?

ANA titer and pattern returned negative.
Not sure why my general doctor sent these tests but LAMBDA returned low as 2.41 on the scale of 6-26, KAPA returned normal.

blood was taken for exome sequencing and they will check sodium channels and the ATP2A2 mutation also.

Started anotibiotics for the blastocystis parasite, hoping that will help with my on going diarrhea.

"Not sure why my general doctor sent these tests but LAMBDA returned low as 2.41 on the scale of 6-26, KAPA returned normal. "

Madmax80, lambda and kappa light chains occur in two contexts. All antibody molecules contain two identical light chains (either lambda or kappa) together with two identical heavy chains, which come in five different classes. As far as I know, variations in the proportions of antibodies with lambda or kappa light chains have no clinical significance.

Both lambda and kappa light chains can also occur free (not as part of antibody molecules). Elevated levels of either can indicate a range of health problems.

I doubt that the fact that your free lambda level is low but free kappa is normal is a matter of concern.

The information here might help you to discuss this with your general doctor Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies.

What I am finding about blastocytis is that it does not require treatment. If you are given metronidazole or Tindmax for it be advised that these two antibiotics cause PN.

More at this link:
Blastocystis hominis infection Treatment - Mayo Clinic

I suggest you read the whole site on this subject as well as this page.

Thanks mrsD. I am given metronidazole 750mg thrice daily for 10 days. thing is about blastocystis is that if no other visible cause is causing the diarrhea, then it should be treated. There are times I see that everything I ate just went out, almost as is.

Any advice on the cold and sweaty palms and feet? especially when exposed to even slight colder temperatures? and this is Israel... it's very warm outside, but A/C in the office..
When my palms are at normal temprature it feels so much better.
I used to like the cold weather so much.. hated the hot temperatures as I'm sweating like hell. Now, I dont mind sweating at all..

I'm also feeling my mouth is very dry for the last couple of days, might be the tension though.

Thanks for all the support.

That is a very high dose. Metronidazole has been a PN trigger here for some posters.

Chronic diarrhea may respond to Metamucil (Psyllium) daily. This acts as a sponge to sop up toxins that may be produced in gut from bad bacteria, etc. I had a GI specialist suggest this for me
many years ago.

Use our search function on page 1 here to find the older posts from posters who are no longer visiting here.
"metronidazole" or "Flagyl" keywords should bring up some older discussions.

Minor updates
 

Vitamin B6 status 23 on the scale of 9-27. still waiting for vitamin b1 and e.
exome sequencing is WIP.
Done with antibiotics
Diarrhea has nausea stopped.
I saw a new neurologist, his conclusion was that my neuropathy is light, but the anxiety levels are very high. The meeting with him was a relief. He did mention that the familial dysautonomia mutation sounds interesting.
I have been wearing sandals the last two weeks and that is helping me the burning feet, I do still have pain episodes, but less.
I stopped the supplements as I thought it might have added to the diarrhea and nausea. I might try to take the ALA again.
I saw a skin doctor who is also a genetic specialist. They will review the skin biopsy taken and asked they look for a ATP2A2 mutation in the exome sequencing. He wants to rule out darier disease.

So, more to come. I'm feeling good less stressed.

Vitamin E and B1 are in range also.

I'm still waiting for the exome sequencing results.
Meanwhile, I have started to try some supplements and wanted to hear your advice.
Started ALA 600mg for a week, and for the last two days doubled to 1200mg.
250mg grape seed extract
100mg phosphatidylserine - trying.. for the ikbkap muation i carry.

I'm vegetarian. What about omega 3 supplements and SFN? Can you think of other supplements I should try? Should I try to increase the dosages?
My symptoms continue - burning feet at times, pain in the hands fingertips and cold hands. I'm also feeling some vibrations above the knee and below the hip of my right leg. constant tinitus on my left ear, and sometimes on my right.

I would try taurine 1000mg a day for the tinnitus.
Taurine is in most meat foods, and you don't eat animal sources.
Benefits of Taurine | Life Extension

The omega-3s are very important. There are vegan versions with EPA and DHA if you won't use fishoil/krill oil.

Methylcobalamin is a must for vegans. There are many YouTubes that discuss this.

Flax oil is metabolized to EPA and DHA, but not in large amounts like in women. So if you use flax oil, you may not have enough DHA and EPA for healing (males about 4% convert, and females 20-25% convert because they furnish fetuses which use these Omegas for nerve/brain growth.)

Thanks mrsD.
I just briefly read about taurine and will order it. I do take Methylcobalamin 1000mg twice a week.
Which omega 3 would you recommend? any specific brand?
What about the Grape seed extract? I was hoping it might help with my cold hands, what's the dosage i can go there?

Thanks again!

Just Google vegan DHA and EPA. The EPA sometimes thins the blood and improves circulation.

I use Krill oil myself now, but I used fish oil 3 times a day in the past. I take one 500mg Krill oil daily now.

There is much less EPA and DHA in these vegan types than real fish oil products:

Amazon.com: Deva Nutrition Deva Vegan DHA-EPA Delayed Release 9 Count: Health & Personal Care

So these are more pricey than fish oil. Looks like 1/2 of the content in the vegan product. You should start with 2 a day of the vegan one.