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February 5, 2013 at 9:13 am in reply to: CBS gene mutations being investigated in Ehlers-Danlos. #3393
I have two CBS mutations. When I looked the CBS genes up it was noted they are being investigated in…. Ehlers-Danlos!
CBS gene mutations are involved in methylation.
What is “The Methylation Pathway”?????:
rs234706 – CBS C699T (Risk Allele: A) “Being investigated in Ehlers-Danlos syndrome”
rs1801181 – CBS A360A (Risk Allele: T, 23andMe: A) “Being investigated in Ehlers-Danlos syndrome”
rs2298758 – CBS I278T (Risk Allele: G) “Being investigated in Ehlers-Danlos syndrome”
“CBS Gene: Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.”
This is a Gene test for Marfan/TAAD which is listed under the heading “Ehlers-Danlos” and it includes CBS.
Genes on this test: ACTA2, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, MYH11, SLC2A10, SMAD3, TGFBR1, TGFBR2
Read more about CBS mutations:
Anyone else have CBS mutations?
Dr. Diana, do you think the sulfur load could be similar to a barrel effect like with histamine? Maybe some patients who haven’t done well on Diamox have CBS mutations and are already over-burdened with sulfur. I wonder if they limited other sulfur sources and got their methylation working better if they might be able to tolerate the Diamox? Hmmmm…. I haven’t tried it yet because I’m so allergic to… sulfa antibiotics but maybe a trial under my allergist’s supervision will be in my future after all. Thoughts?
Thank you very much for posting this SweetFeather.
Using 23andme my wife found out she is homozygous positive for the C699T CBS mutation and the A1298C MTHFR mutation.
It’s very interesting to me to see that CBS is being investigated for its role in EDS. I wish there was more of a description re who/what/where is being investigated, but I guess it will be published eventually if any of the investigations are fruitful.
I just want to clarify something I saw. I think there are two different ways that CBS mutations can affect the methylation cycle are being mentioned in your links though.
The link relating to the Marfan Syndrome genetic test I believe is (partly) testing for a mutation in the CBS gene that involves downregulation of CBS and can cause elevated levels of homocysteine and is seen to be responsible for a condition called Homocystinuria that has overlap w/ Marfan (see here, http://www.ncbi.nlm.nih.gov/books/NBK1335/, and here, http://www.ncbi.nlm.nih.gov/books/NBK1524/ – I arrived at these links from the Marfan testing link you posted). I believe those studies refer to the 833T>C and 919G>A mutations of the CBS gene.
The mutations referred to by Dr. Amy Yasko are Y233Y (C699T) and A360A. Yasko says that these mutations involve an upregulation of the CBS gene and that “It’s not surprising that in those with the CBS mutation it’s common to see low levels of homocysteine, cysteine, or cystathionine, due to the rapid conversion to taurine.”
It seems like if these mutations are part of the problem and need addressing, then the directionality of regulation is important.
We’ve only just started on looking into treatment for this, and are planning to read through all of Yasko’s book.June 24, 2012 at 5:05 pm in reply to: What tests can I get to investigate possible CCSVI? #2479
there’s also intra-venous ultra sound and plain old catheter venography too.
also, correcting myself, i think CT scans actually are used to see if the atlas of certain spine bones are causing a narrowing of the vein as well.June 23, 2012 at 10:17 pm in reply to: What tests can I get to investigate possible CCSVI? #2478
Hi POTS, my wife was tested for CCSVI at Stanford and the Hubbard Foundation in San Diego. Those facilities both use a functional 3T MRI/MRV/MRA to image the anatomy of your vessels (with particular focus on internal jugulars and azygos), but also test the flow of blood through those vessels as well. Stanford, and others, also perform an ultrasound of the neck area, not transcranial. There are some facilities that use only MRI or only ultrasound. I am not aware of any that use CT, but I haven’t looked everywhere.
Hi George, I’m not entirely familiar with the full Haacke protocol, but my wife has had similar protocols for flow mri/mrv/mra done at Stanford and the Hubbard Foundation in San Diego. She has CCSVI, pusilar tinnitus, pain at the base of the skull, and extreme vertigo just like you. Her heart rate also drops very low as well.
My experience has been that the docs we’ve seen are not really looking for external communicating hydrocephalus. My understanding is that ventricle enlargement would not necessarily occur in external communicating hydro since there is not an obstruction between the ventricles. My sense is that most docs looking at hydro stop once they see no evidence of ventricle enlargement. This is unfortunate since it could be adding to the number of undiagnosed patients with this health problem. In any case, I don’t think the Haacke protocol (or any of the ccsvi protocols) is focused on hydro, but more on CCSVI instead right? I suppose it’s going to pick up on it given how extensive the brain imaging is in it. However, you may be better off trying to find someone that could focus on that particular issue.
I know that in my wife’s case there appears to be extra fluid on top of the brain (to my eyes), however, no one has read the imaging in that way. I can tell you that a positive response to treatment with Diamox is considered by some to be an indication that hydrocephalus is present all by itself. Are you taking Diamox? She’s responded well to it, you might consider talking to you doc about it if you haven’t already.
I have read in places that normal pressure hydro can be episodic such that it may not show itself until a patient is lying down during bedtime at night. However, I’ve not heard of this in other forms of hydrocephalus. Good luck!
thanks ourfullhouse. can you tell me where you found that (if it was online)?
oh okay, thanks.
we were told by one of our docs that you could take calcium carb instead, that they would do substantially the same thing.
thanks for sharing ourfullhouse.
yeah it sounds like we need to up my wife’s carbonate dosage. does anyone have knowledge/experience taking both calcium carbonate (tums) and sodium bicarb at the same time? also anyone know of a benefit of one vs the other?
hi ourfullhouse, do you mind sharing how many mg of bicarb are in your pills and how many mg of diamox you’re taking?
my wife can’t seem to stay alkaline even though she’s only on 62.5mg of diamox 3x day. now she’s actually trying calcium carbonate instead of bicarb (anyone else have any experience with this?). she’s also trying pretty hard to avoid acidic foods. i have a feeling that the propranolol isn’t helping this issue and we’re working on taking that down too.
Yes, saw it, and thank you! I have really, REALLY fought the acidity issue AND my potassium also went south about month 8 on Diamox. Could those RX potassium pills be any more huge? Ugh. Can’t wait to see part two of this! If there is something besides bicarb to help with this issue, that would be AWESOME! As it is, I am taking 12+ bicarb tablets a DAY and “only” two Diamox pills a day (one AM, one PM).
It was also good to hear someone say that when we sometimes think the Diamox is not working it probably isn’t the Diamox, it is the acidity. I have kind of gone round and round with this issue, trying different doses and then recently just stopped the Diamox altogether for about 6 days (trying to see how long it would take for my body to “notice” the Diamox wasn’t on board anymore, as far as symptoms, etc.). I was surprised I didn’t have a headache right away. But, on day 6 my world came crashing down and then I was BEHIND the problem(s) and my body was so ticked off and inflamed I had to go on prednisone for a few days. So, word to the wise, don’t go off it even if you don’t think it is helping!
I recently stumbled upon and wondered about the Hubbard Foundation. My family is from San Diego (where Hubbard is based) so it stuck out when I saw that they diagnosed ccsvi. I noticed there is a ccsvi conference in san diego being put on by the Hubbard Foundation. Dr. D, is that were you ultimately had your imaging done and read?
I have been recently diagnosed the POTS. I am feeling better most days with medication
Midodrine, Mestinon, Florinef, LDN. What you say about CCSVI causing POTS makes so much sense to me.
Since my illness began, July 2, 2011, I began having daily migraines along with the other symptoms of POTS, the overwhelming fatigue being the most troubling. But I also hear and feel a loud swooshing sound as the blood goes through my neck. Very disturbing sound/sensation.
Without disposable cash on hand, but with good insurance, what is the best way for me to get tested for CCSVI?
Hi, With migraines and fatigue, I wonder if you have external communicating hydrocephalus? Does the base of your head, radiating down your neck hurt? Any nausea, dizziness, sensitivity to noise/light, ear aches, tremors — all worse with straining (valsalva)? That would indicate a need for Diamox. I’ve never heard of a patient HEAR their CCSVI before, but plenty of folks hear the increased pressure if it affects their ears. Hmmm. PLEASE be sure your doctor checks that out, just to be sure it isn’t related to your carotid artery, or cavernous sinus, OK? To be checked for CCSVI (although I wouldn’t recommend TREATING the CCSVI, especially if your cytokines are not yet under control) you can have an fMRI (likely the most reliable test — just google fMRI CCSVI locations), but an MRV will usually also show it (but the radiologist won’t be able to tell you — the images must be read by someone familiar with CCSVI), and in an experienced hand, a sonogram can usually pick it up — especially if there is blood flow BACKWARDS in the vein. When I went to be evaluated, I knew I wanted Dr. Haacke to read my images, so I googled him and the Hubbard Foundation to get started. Then I SPOKE to the interventional radiologists and researched the centers to find out who had the most experience, etc. Yup, nothing replaces a little bit of homework! Let us know, OK? 🙂 Diana
Dr D, I just watched your video on external communicating hydro video and I noticed that you mentioned that you and your family get motion sickness easily and that this is a symptom of hydro. My wife, who was on diamox but also was pretty acidic, went to the er for a terrible case of vertigo and motion sickness. Do you ever get vertigo with your motion sickness?
Has anyone ever experienced vertigo, nausea, and loss of hearing/ringing in ear while taking diamox? My wife woke up yesterday with severe vertigo/nausea and spent most of the day sick to her stomach and hasn’t left the bedroom still. This morning she woke up with loss of hearing and ringing. We’re working with her doctor to address this of course, just wondering if anyone else has had this and has had any luck treating it?
I’m not a doctor, but I would think your reaction to the toothpaste brought on the headache you experienced/are experiencing. Just because Diamox takes care of CSF headaches doesn’t mean you can’t get a headache for a different reason. So, don’t be too quick to judge the Diamox or drop it is what I am thinking. You need to do what you need to do, of course.
Do you have an epi pen? Sounds like you NEED one!
Pain meds don’t do much for migraines, it is the nature of the beast. For me, the best I can hope for is that pain meds help me not care as much or help me relax a bit/sleep, etc. Have you ever tried a high dose of caffeine when having a migraine to see if that helps? I have caffeine pills on hand as that seems to the the thing in Excedrin that really helps me with a true migraine (when/if I get one, which I don’t very often anymore).
Now, I have been thinking/hoping that the Diamox is the “cure” for my POTS, but I am now seeing that several symptoms are still there, even though several are gone/better. And, then the next pieces of the puzzle with the cytokines that Dr. Diana has explained in Part 2 of her theory, that will hopefully help too.
I would be curious to know what all other people are here are taking to treat their POTS, besides Diamox? Is anyone taking an anti-depressant to control the re-uptake of norepinephrine, and if so, which one?
It means a lot to me to have somewhere to “go” with other people who share this same crazy combination of illness/syndromes/genetic defects/whatever you want to call it, lol. Family and friends, as much as they want to listen and be helpful, just don’t understand.
Yes, yes yes! Diamox doesn’t cure POTS, but it is where we need to start. Otherwise, we are just bailing in a leaky boat! YES! Epi pen! And a mast cell stabilizer (Cromolyn sodium). I take a wee bit of Cymbalta for hyperadrenergic POTS, and since us hyeradrenergic POTS folks spit out SO much nor-epi, lots of magnesium citrate is a MUST! Mine was SOOO bad, that I had to get on Xanax, but don’t need as much now. That is very difficult to get off of, but my doc was shocked when I was able to go DOWN on the dose. And YES! The next step coming up will help us even more! We may not be able to get rid of EDS and we may have to grapple with some POTS, but if we can just get it down to a nuisance, I for one, will be thrilled with that! Our kids have SO much hope now, especially if we watch their head circumferences from a young age. My son, as many of you know was at death’s door for three years. He was too ill to even be tutored. Now he is rarely symptomatic, and it is life changing for everyone. My daughter swore her POTS was gone forever, until we took her off of the meds to show the doctor her blood work and tilt table. Whoa. Yup — the meds were taking such good control of it that she didn’t even notice it! (Ahh, youth!). They seem to bounce back so quickly. What’s that in the air? HOPE, my friends. For all of us! I just heard from a patient who was dumped in a nursing home. She is out of her wheelchair and getting her own apartment now AND A JOB! They had written her off. Such a great ending to an incredibly sad story. It gives me goose bumps…. 🙂
Dr. Diana, can you explain what the cymbalta and magnesium citrate are doing for your hyperadrenergic pots? Some of my wife’s docs have offered cymbalta over time as a med that might help her, but I never understood why it might (although I understand their reasoning may be different than yours/your doc’s). And, I can’t find mag citrate described as anything other than a laxative.
That’s very inspiring news about your children and the nursing home patient indeed!
shnoogals, i believe others on the forum have posted that the numbness/tingling subsides after a while. my wife is also on diamox and is experiencing some tingling. she was initially prescribed the 500 mg capsules as well. her’s were the extended release version (i’m guessing that’s what you have too). we immediately called the prescribing doc and asked that they call in the other form of the med – which they did. i believe Dr. Diana suggested that the regular release tablets work better for her (and others too). that’s what my wife is taking now, and as you’ve heard, you can adjust the dosage with those easily by breaking the tablet. not sure what a normal dose is, but my wife worked her way from 62.5 mg 3x day to 125 mg 3x day. She’s sticking with that for now.
So I had an appointment with the eye doc for some issues I have been having. I asked her if she could do high resolution photos for Dr. D to look at. I had Dr. D’s poster from her talk saved on my iPad so she could read about what the study was about and why I was making that request. Here are my eyes. She said they looked pretty good, aka normal. Will be interesting to see what Dr. D says.
Hi Palomino, This is why eye doctors have missed this in the past (me included!). This is the “typical” magnification for a fundus photo, so you can’t see it. Some of the vessels must be magnified MUCH more than what we would do for a typical eye exam. THEN you can see the problem with the vessels. I’m using a special camera for the study that allows me to magnify the heck out of the vessels, use special filters if needed, and THEN it can be seen. Just like the examples on this site from the talks I gave. You’ll see some of the veins look like sausages on a string, hinting at poor venous drainage. I saw some other things, too that will be quite telling. I’m pulling it together for publishing it in a peer-reviewed journal now. Lots of work to do!
Thank you for sharing this!
Dr. Diana, is there a particular type of imaging machine or method that we could ask for in our area that would show the level of detail required? Also, how would you go about getting the Rx for this? Or even go about getting it read? We just saw an optometrist who refused to do any sort of magnified imaging unless she saw something irregular in her examination.
Hello, my friend. Of course I can’t treat or diagnose your wife over the internet (see disclaimers), but I do have a few thoughts on this. The pain you describe does sound like mild hydrocephalus, so I wouldn’t give up, yet! I think you hit the nail on the head with your thought of drug interactions. Florinef made my intracranial pressure, and resulting symptoms MUCH worse (which was how I cinched the suspicions of mild hydrocephalus. Propranolol will contribute to acidosis, but I think that wouldn’t be a huge issue so quickly (but you don’t want it to become an issue, either, so caution is in order there. Since you have Part 2, you may have seen the section on neurogenic shock, where our BP and heart rate can drop simultaneously while we are on our backs (due to compression of the vagus nerve). If propranolol is in her system, she may be less able to avoid shock. Propranolol is a short-acting drug, so with your doctor’s OK, you may want to try discontinuing that drug, at least for night time. Then she may be able to go UP on her evening dose of Diamox. The evening dose is the most important, since we drain CSF and blood from our brains more poorly at night time. If you have a machine to check her BP and heart rate, it would be a good idea to be sure it is not dropping too low at night time. The Florinef may be adding more CSF and blood into her head, but when she is supine, she is less able to drain any fluid, resulting in more compression on her vagus nerve. Any attempt by her body to raise her heart rate to compensate may be impossible on propranolol (and her evening dose of Diamox is likely too low to compensate for the increased fluid from the Florinef. Hence, her symptoms get worse, or not better. Does that make sense? I would recommend that she work with her doctor on discontinuing Florinef for a while, and stopping any propranolol that could carry over until bed time. Then consider a night or two on a higher dose of Diamox (maybe 125mg or even 250mg) to see if that doesn’t stop that headache overnight. What is hard for some physicians to grasp is that we are trying to address the CAUSE of the dysautonomia, not just minimize the symptoms. And if that regimen is working for her symptoms, then work closely at monitoring her CO2 levels (she’ll need to stay above 22) and her potassium levels. Is she also taking a good amount of magnesium citrate? That’s important, too. It sounds complicated — and it can take some fiddling to get the best dose for her, but once she’s got it, she’s got it! Will you keep us posted? 🙂 Diana
Thanks so much Dr. Diana! That was a very helpful explanation about the way these drugs might be interacting.