Birdlady

Wow congrats. That is soo exciting! This is why so many of us tell people to just give GF a try for awhile and see how you feel! The blood tests are notoriously wrong unfortunately and so many only go by those. My husband did Enterolabs and his results were like over 150. It was shocking to us.

This is why I review my lab work and MRI/CT/XRay reports etc etc. Of course I can't look at a scan and made heads from tails with it though...LOL All looks like blobs to me.

I would let your doctor followup and do some more investigation. I'd be scared to have anything removed from my brain unless I knew for sure. Brain surgery is no small thing!!

I think I'm the person issie is referring to! haha I have 2 COMT mutations (V158M and H62H) and I also have a common synonmous MAOA mutation (R297R), but I thought Issie would have them too and she does not! All of this is so very complex where one thing cancels another thing out and then there's the concept of epigenetics too. There are many other COMT and MAOA mutations I do not have that are far more damaging to the function of those enzymes.

Zap I see from your signature you are researching this aspect, so feel free to get a hold of me. I'm fascinated by it too.

Thanks for posting the link to the full article.

Ugh studies like this make me sad only because I know I'm so far past this.

Yep this is exactly how I am too. I love it when I have goosebumps! haha

heat heat and heat. used to be a hot day, now its any room over 72

I usually say I'm making up for how bad I feel inside or I just say thanks and nod my head..... Depends on who is saying it to me.

There are studies that talk about how/why this is happening. You have to read the full study though. I'll try to take a look around here and I'll post them here if I find them. There's that one about mice and the healthy subjects they induced POTS in, that I've already posted in the other thread. There are also others though I've come across that the issues are only when standing because of sympathetic stimulation or something like that. When you sit down, the parasympathetic nervous system kicks in, so there is less NE traveling through the synapses any way thus the decrease in NE clearance doesn't become an issue. Hopefully I'm making sense and not botching this...

From this study:

"Second, although norepinephrine spillover and clearance are similar in patients and normal subjects when supine, spillover fails to increase and clearance actually decreases with upright posture in patients."

"Supine norepinephrine was also greater in patients. Although the increase in norepinephrine spillover with standing was similar in patients and control subjects, the decrease in clearance was greater in patients than control subjects, indicating that much of the increase in plasma norepinephrine was due to a decrease in clearance."

Rama, the thing is NET deficiency = higher than normal NE levels almost like Pheochromocytoma. The difference is the researchers that link NET def to hyper pots mean that this NET deficiency only occurs while standing. Read this and you can see the connection http://www.ncbi.nlm....pubmed/17102094

I had to get away from facebook. I am on multiple health groups on there it was driving me literally insane. Here I can choose to look at threads that interest me. On Facebook, my entire news feed was of sick stuff. It was too too much. I took notifications off for everything, so that has helped.

The HPA axis dysregulation theory has been around for some time especially in the CFS communities. All I can say about it is what I've been through and I wasted about 2 1/2 years on trying different types of hormone replacement. In the end, if you have HPA axis dysregulation, I don't really see what you can do about it except replace the end result hormones you are missing. The HPA axis does soo many things and I don't know how we could ever replace it all.

Here's a study you may find interesting.

http://jcem.endojour.../86/8/3545.full

Even though HC did not cure my POTS, wow did it bring me up to a much higher level of functioning. I really think I was dying there for a while.

It's very fast right now. Once it is received by the lab and if there is sufficient DNA in the sample, it's only taking about 1-3 weeks. One person got their results in 7 days. Another got them in 16 days. I really need to get my dad's spit...lol I have a kit waiting here for him, but I keep forgetting! Doh!!

diamond, that is true! I was never very good at taking orders either...lol

I just saw that one study. I wish they had tested the whole NET gene though because we now know that mutation is only unique to that one family.

The reason why I said there is no way a POTSy could be in the military is from my own experience with symptoms. I cannot carry heavy objects. Carrying even a small sized pack on my back is impossble for me. I also cannot crouch down and get up real quick. I can't be in stressful situations at all... Essentially there is no way I could even make it past basic training and the strict schedule and constant stress would kill me.

When I'm experiencing really high HR's (165+) my thinking and decision making abilities go right out the window. I become jumpy, jittery begin to tremble, and I have terrible shortness of breath. I can't do any fine movements without being very clumsy and I trip over my own feet. I drop stuff. I look like I'm on drugs. I also know I'm not feeling well when I'm rambling on, talking a mile a minute. None of these things are good in the military, so I'm just looking at this from my perspective.

Perhaps I should say, there is no way I could be in the military.

I took Sam-E at one time, but I was not doing very well at that time with various other issues, so I can't say either way what it did for me. I used it because I saw this study.

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers.

http://www.ncbi.nlm..../pubmed/3961029

No word from any of the researchers/docs. I'm thinking they aren't going to get back to me on this. Where should I go from here?

There has to be more to it. I re-read the one study where some of the family members with A457P did not have POTS and it did not test their NET function. It just tested their supine NE, BP, HR and compared it to standing NE, BP, HR....

I started looking up some of the other people who share this rare allele with me on GEDmatch.com and according to some of these people's FB pages, they look very healthy. Now I look healthy too, so this is not a good way to screen. But one guy was in the military. There is no way a POTSy could be in the military.

I've never had any of the "POTSy" antibodies checked. I've had others done for thyroid, adrenals, lupus, Sjogrens and they are normal. So many pieces to this puzzle and not enough experts out there understand it...

I'm thinking there has to be something in addition to NET deficiency. For instance, one would expect everyone who takes SNRI's to get POTS if NET alone was the causal mechanism. EDIT: Actually this may not be true, reboxetine used in the study is actually a very unique NET in that it binds only NET. The other SNRI's bind other parts of the ANS that might balance out NET inhibition and not cause POTS. Actually reboxetine is having difficulty getting approval in the USA because of its uncertain therapeutic benefit and potential side effects, (which probably includes drug induced POTS).

I believe there is also autoantibodies involved. 15-20% of POTS patients have ACHR antibodies. There's probably other antibodies as well.

I don't know what to think about it all. He is obviously feeling better because he stood for that TV segment and then it looks like they played a song... I would have been a mess. Touring messes up healthy people. You see singers all the time having to cancel because they get sick on tour and can never recover properly. I really do not know how he is doing it without meds. Good for him. I'm jealous.

I'm a weird one who is on HC and it didn't do anything for my POTS. My standing HR's are just as bad, if not worse nowadays. 160 is the normal for me....lol But there was a night and day difference when I started it. All of the fatigue, nausea and general cruddy feelings went away. An Endo would never have let me take HC... I am under the care of a natural doc.

I'm not real sure how accurate saliva tests are though. I've seen a lot of weird results.

I don't think much will change for me.I will always keep trying to search for answers though. After many failed treatments/medicines, realistically I just don't see myself getting much better by man. I'm already going on 12 years with POTS and when I really look back and think about it, I've had signs of POTS since at least age 8. They just weren't as severe as now and I didn't understand it was abnormal to feel the things I felt. I thought it was normal!

I keep praying and I truly believe the only way I will be healed is by God. He's the only one who has the ability to take all of this away from me. Even if a doc has some treatment, it is still only a treatment.

It might be possible that even with A457P one could have normal NET expression. What I mean is, maybe the mutation only achieves 98% reduction in NET protein if an environmental cue also triggers it. Now if a person had that mutation and they measured their NET protein to be 98% reduced and they still did not have POTS then that would be confusing.

But really the study where they blocked people's NET protein and it produced POTS pretty much sealed the deal for me already. There's no mistaking that.

Yep you are right that the normal ones probably did not have decreased NET.... I'm going to have to take a look at the original A457P study again and see what was tested.

SO if this is the case, NET defiency, wouldn't people who use SNRIs have pots symptoms?

In the study that's essentially what happened, yes. They gave them the SNRI reboxetine and it caused a POTS like syndrome. I have no idea how much 8mg of reboxetine is in comparison to a normal dosing someone would take on a daily basis.

We have to remember that not all POTS is NET deficiency though. I don't think PD POTS would fit in this category, but someone correct me if I am wrong.

Ok thanks! I have been looking at so many different studies I can't keep them straight anymore.

If it only takes a 34% reduction in NET protein, then I think V245I is very close to that. Now what doesn't make sense is how would those with A457P which is >98% reduction in NET protein, not have full blown POTS. Hmmm

It was in the epigenetic POTS study. They posted a picture where they calculated the NET concentration for the control and POTS patients and found POTS patients in their study had about a 34% reduction of NET protein.

When I say mine isn't all the time, don't think I go days or weeks without POTS. I am symptomatic every single day, but every once in a while when I stand my HR's are 80-95. Usually they are 160+ so I'll take what I can get....haha

It's ok jangle. My bad too. It was just a misunderstanding on both of our parts. I want this thread to be a happy place where people can ask questions because this stuff is soo darn confusing. lol

I'm talking only about the study showing that blocking NET in healthy volunteers produced POTS OI and the study demonstrating that POTS patients had 34% reduction of NET expression.

Yes I agree with you too. This study really seals the deal for me! Do you remember which study said that POTS patients had 34% reduced expression of NET? I might have missed that one.

I'm not really sure if they tested NET expression in the healthy family members with the mutations. That's a good question! I'd have to look over it again.

You have to remember that not all of the family members in that first study even had POTS yet they were carriers for A457P. I don't think it was definitive. Even the researchers said there must have been other things to account for the phenotype. If A457P really does cause >98% decrease in NET function, then why aren't all of the family members affected by POTS? It certainly raised a lot of questions and they started doing more research. I think the studies where they take healthy people and induce POTS is more definitive so that's why I posted them for Rich to take a look at. No need to be condescending here. We are all learning and desperate for answers.

""Furthermore, in the current study, family members who had the mutation also had some of the physiologic and biochemical abnormalities detected in the proband and her twin sister, but none had the full-blown syndrome. Thus, other genetic or environmental factors must have contributed to the phenotype in the two affected women.""

The first study is pretty definitive that NET deficiency and/or mutated NET proteins is the cause of POTS.

Rich,

Since they found those twins, they have done a lot more research on this gene. No one else has the exact same mutation these twins had and you are right, some of the other family members of these twins who carried the A457P mutation had symptoms of POTS, but did not the have full-blown disease. However, I still think the NET deficiency theory is a good one especially for those people who have already been at this for years and fit the profile.

I'll be honest, I never looked much into it before I found this gene because I did not understand enough about genetics. I also thought by now I would have cured my POTS with other various treatments/ supplements and that hasn't happened yet. So for me, I am just going down the natural progression of research. I've been at this for a long time, so genetic testing for some on here is probably not appropriate yet because they haven't ruled out other simple things.

I was fairly certain NET deficiency is listed on the dinet set as a possible cause.

The studies that really caught my eye were these two. There are drugs which inhibit NET and when they do this in healthy people, they essentially get POTS. That's pretty significant IMO.

Selective Norepinephrine Reuptake Inhibition as a Human Model of Orthostatic Intolerance

http://circ.ahajourn.../105/3/347.full

Here they tested mice. The significant part of this study for me at least is that they were normal while resting. I am pretty much normal when I sit.

Norepinephrine Transporter–Deficient Mice Exhibit Excessive Tachycardia and Elevated Blood Pressure With Wakefulness and Activity

http://circ.ahajourn...10/10/1191.full

Aww thanks Issie, That's really nice of you.

I'm hoping I ever hear back from them. haha! My doc said he won't talk to me about this until my next appt... I'm not sure what to make of that. Took them a week to call me back. They've pushed back every single appt I've had with him so far, so I'm skeptical this one will even stick. Blah just sort of complaining right now. I just feel like these docs really do not care.

I wait until July 30 to hear what he has to say.

Yes sometimes I am normal and I've asked myself this same question too! Usually my HR's are significantly lower when I'm tired or when it's near the end of the day. But then other times I have 100bpm increase when I stand, so go figure that one out!! hahah! I don't even feel faint when I stand though, so who knows what is going on in my body. I wish I could hook myself up to a machine, like what they do for cars when the check engine light comes up, and it tells you exactly what is going on! lol