Possible Cause For Pots? Mutation On Net Gene

[diamondcut]

Dana - who wants to be ordered around anyway!!! POTs or no POTs

Sorry had to say that, dont take authority too well.... I think it comes from a lack of respect for most Dr's!!

[Birdlady]

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

[diamondcut]

I have sent my 23 and me sample back today (after taking me nearly 15 minutes to fill it up with what i can only call spit lol), how long does it take them to give you your results back?

[Birdlady]

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!!

[issie]

Hmmmm, not sure where to tell you to go with that info Dana. Maybe a geneticist - could run the whole panel on you. Would this change the way you treat yourself? Sometimes, if you suspect an issue then maybe just seeing what the treatment would be and trying it - may be good enough. I know money is tight for most everyone these days. If you could get someone to address the fact that this may be your problem and see what to do - if it were - then the help is what's more important - then the positive I.D. of the problem. Although, after having searched for so long ----we want to know the reasons.

Issie

[RichGotsPots]

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.

The symptoms of pheo are very similar to pots so of course whose to say they didnt cause pheo and not pots? Only thing that is sealed is the pots has something to do with NE issues. But really how do they know its not a sensitivity issue? Many people develop these odd sensativities to light, noise, heat, food, and many more things, so maybe at certain time people get this odd sensitivity to NE because of "____" (something mysterious...)

[ramakentesh]

This study put NET deficiency as a possibility back on the table. Since the studies in 2000 where the findings were not replicated it fell off the tables to some degree:

http://www.ncbi.nlm.nih.gov/pubmed/18187607

This phenotype is remarkably similar to POTS it some patients. Note that NE levels were not overly elevated.

here we find MIBG reuptake is reduced in 4 out of 20 POTS patients - interpreted to mean that there is cardiac denervation but QSART was normal (what ever that means) and MIBG can also suggest that NET is not functioning correctly via various mechanisms:

http://www.ncbi.nlm.nih.gov/pubmed/19687022

Certainly these studies can be - and have been - interpreted by some to indicate NET deficiency rather than cardiac denervation. MIBG is like a non active isotope that is identical as far as the body is concerned to NE and can be used to measure how much NE is uptaken by NET (where expression is dense).

Further evidence of NET deficiency WITHOUT the presence of an actual genetic mutation can be found here:

http://www.ncbi.nlm.nih.gov/pubmed/19808400

here some of the NET levels were found to be quite low in patients tested.

Think of it as this - NET would upregulate the effects of NE in the heart and hands/feet, but downregulate its effects in the brain, chest and stomach through its effects on cerebral alpha 2 receptors (the ones that vasodilate to put it in crude terms or suppress sympathetic outflow). it may also just effect cerebral autoregulation by unknown mechanisms. it may cause Ne levels when spiking in the CNS to increase sympathetit supression - resulting in worsening dizziness perhaps after a fright or scary situation. it can be interpreted potentialy to explain LOTS of the symptoms. it could even explain chronic hypovolumia via dopamine effects in the kidney???

I emailed the original proband with genetic NET deficiency in the 2000 Shannon study and her symptoms were classic POTS. They were - subjectively - indistinguishable from mine and many others.

Angiotensin II may also reduce NET expression or effect NET reuptake. So the finding of some impairment in NET may not automatically suggest NET deficiency in all cases.

Dana - interesting - i wasnt aware that other mutations have been implicated in POTS. Genetic mutation is a scary thought so I guess in some ways I hope yours is epigenetic potentially rather than genetic

jangle - remember that the autoantibody titers for a3 autonomic receptors in POTS were VERY low - barely above baseline. Some doctors arent overly convinced by Mayo's findings and I know that Mayo continue to look for further autoantibodies.

issie - be careful with medications that have effects on multiple cns neurotransmitters. These can be dangerous. Especially in POTS where the results are unknown.

SNRIs - some do well on them. Id tread with caution given this very mechanism is implicated in POTS at least for some.

Rich - it must be a language barrier

[ramakentesh]

Apparently NET function is also regulated to a degree by hormonal changes in woman during their menstrual cycle:

http://hyper.ahajournals.org/content/51/4/1203.full.pdf

[ramakentesh]

http://www.ncbi.nlm.nih.gov/pubmed/15533861

there is another study by Dr Jens Jordan on NET deficiency but i cannot find it.

[ramakentesh]

The symptoms of pheo are very similar to pots so of course whose to say they didnt cause pheo and not pots? Only thing that is sealed is the pots has something to do with NE issues. But really how do they know its not a sensitivity issue? Many people develop these odd sensativities to light, noise, heat, food, and many more things, so maybe at certain time people get this odd sensitivity to NE because of "____" (something mysterious...)

because when there is no reuptake it effects different areas of the brain and body paradoxically by either increasing or decreasing the response to NE?? perhaps some sort of reduction in sympathetic activity in the brain results in some kind of reflex vasoconstriction (which may have been found in unpublished data) - which like in migraine aura - effects various areas of the brain resulting in migrane-type aural symptoms?

[Birdlady]

Thank you Rama for all of these studies. I had seen a lot of these, but did not bookmark them at the time!

From what I've been reading, you are right that different parts of the body can be affected more by decreased NET function. The heart is more dependent upon NET clearing out NE than say the vascular system. Perhaps that explains why some of us don't have high BP with HyperPOTS and maybe some of us do for those paradoxical reasons you have mentioned. It seems so darn complex.

http://circep.ahajou...nt/1/2/103.full

"In the heart, approximately 80% to 90% of released norepinephrine is recaptured into sympathetic nerves, making the heart more sensitive than all other organs to impairments of transmitter reuptake."

http://hyper.ahajour...t/48/1/120.full

"One possible explanation for the discrepant sympathetic response between organs is an anatomic difference in adrenergic synapses. In the heart, pre- and postsynaptic membranes are located particularly close to each other.¹⁸ This anatomic feature makes the heart more dependent on NET for removal of norepinephrine from the synaptic cleft. Indeed, a larger proportion of the released norepinephrine is taken up through NET in the heart compared with other organs.¹⁹"

I hope mine isn't genetic, but at least I'd have some answers! Sadly I would be rejoiced to know and I think my family would be interested too. I'd bet money on the fact that my dad has some form of POTS too.

[issie]

Dana, I hope yours is epigenetic too - because if it is - there may be a way to tweak it. But, like you say, just having some answers will help to give a sense of calm. It's the not knowing that is the frustration of all of this.

Rama, thanks for the concern and warning. There comes a point where we have to be willing to maybe be the first POTS patient to try something. Someone has to be the first one . . .it may be the only way we will find the solutions. Of course, I still hope that I can find a more natural alternative . . .but, there comes a time when just maybe more quality of life is what we seek and not necessarily more quantity of life.

Issie

[RichGotsPots]

Dana, cool research about NET and the heart. And I hope there isnt any mutation at all lol

[issie]

bump ---research on SLC6A2. As new info comes to light.