I was diagnosed with PA at the approximate age of 16 by Hematologist. Taught to SI at 21 by GP. Due to sporadic treatment due to relocations, I was just diagnosed with Subacute Combined Degeneration of the Spinal Cord through McGill health in Montreal, Canada.
I ran my DNA through the Impute.me parser, against the UK-Biobank database, and came out with a potential need for medication with B12 higher than 99 percent of the dataset. I do know the risks, but chose to do it anyway, for science.
Does anyone know if there is interest in pooling this data? I'm more than willing to share my PDF of these very rare (some as low as 0.001) mutations.
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ButterflySugarBaby
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I am certainly interested in finding out more about the genetics behind B12D. I have unexplained B12D (possibly functional according to my neurologist) but of course it may just be PA which has not showed up in IFAB or parietel cell Antibody tests. I need alternate day injections to keep symptoms at bay (which no medical practitioners are prepared to support so I do my own at home). I looked for a commercial genetic test that might explain my issues which I could self-refer for, and the best I could come up with was one provided by NGX (a company that provides nutritional supplements based on genetics). They tested one gene for TCN2 (Transcobalamin II) and 3 for MTHFR.
I have RS1801198 - GG which supposedly makes me less able to transport and utilise B12 but they have yet to provide me with the scientific studies that back this up. They did say that 20 - 30% of the population also have this, and that this alone would not necessarily lead to requirement for B12 injections. So I think I'm no further forward in understanding what is causing my issues and I am very frustrated, since without a diagnosis I am left to manage my treatment on my own.
I would be interested to hear more about what you have learned about the genetics behind B12D, how you came to get tested so comprehensively, and what it all means.
Basically, I'm a nerd with a ton of time on my hands. I got a DNA kit for genealogy, downloaded the raw DNA data they had, then ran my data through every sketchy, user-unfriendly data parser that I could find for free or cheap online. In 20 years all of the mine slaves will probably be my clones, and worse, but in the end it was worth it.
Check out impute.me if you have a raw data file. If you use the settings in this picture it will compare your genes with a bunch of people in the UK who have been treated with vitamin B12. The list of genes that it gives will give you something to read if you're bored, and if you're (un) lucky enough, may give you hints about what to Google next.
I wish you the very best of luck, and remember to tell any doctor that refuses testing or treatment to 'Note that in my chart.' They will usually do more tests then, for fear that they messed up somewhere, and a colleague will think poorly of them.
Thank you for this. I finally had my genome sequenced - but am waiting for the mental and physical energy to get into and download my raw data. You've given me a little bit of a boost in that direction. Cheers and wishes for better health.
So, just so we're really clear, I'm not a doctor and this is not medical advice for you. I simply Google stuff and know where to get pretty good information. I think that if I had those specific genes and variations (and I do) I'd self inject until I feel good enough between shots. Match symptoms, and don't worry about the frequency. Expensive urine happens. If you feel low on B12, take a shot. I feel fine on 1cc a month as maintenance, but that's just me. After menopause, if I can go down to 400mcgs of folic acid (including in my diet) that'd be good because of this gene: snpedia.com/index.php/Rs180...
I'd keep getting my homocysteine levels checked. If it got too high, I'd weigh the risk between nerve damage and heart issues. I'd probably up my folic acid a bit and accept the nerves. But that's just me.
Thanks for the reference - having read it, I now understand more about my TCN2 result especially since some studies refer to it differently than others. ("rs1801198, also known as c.776G>C, p.Arg259Pro and R259P, is a common variant in the TCN2 gene on chromosome 22. Note that in older (pre-2003) literature this variant was known as c.775G>C.")
Also the info about folate levels and neuropathy with this genetic variant is very interesting, especially since I'm fairly sure that my current nerve issues are unlikely to be a result of B12 deficiency given my current treatment regime. My serum folate levels are often high (just above max range) but I had not considered this to be an issue until having seen the study you mentioned. The nutritional geneticist I spoke to at the company who provided my test did suggest a homocysteine test although more because of my MTHFR variant than the TCN2 issue. But it sounds like it might be worth the pain of finding a practitioner who will do the test even if I have to pay privately. I would think my chances of getting on via my UK GP would be close to zero.
Mentions a conference on B12 deficiency in May 2022.
May be worth searching on internet for research articles about genetics behind PA/B12 deficiency as this may show people who are researching the area you are interested in.
I looked online for "pernicious anaemia genes" and found several interesting articles.
NORD, National Organization for Rare Disorders (think it's US based) has an article on PA that mentions genes associated with PA.
Some of the details in the article may be upsetting.
Thanks so much! After I wrote this, I checked Google just to see if there were any studies going on in my neck of the world. I found one molecular geneticist who is in my city. My DNA is all over the place, even the police have it because my father is missing, presumed drowned, so I really don't care about security. Anyway, I looked him up, and a decade's worth of his studies.
Wouldn't you know, I have missense variants on the same genes in his latest study. I figured that I would be totally ignored, but I sent him a quick, three sentence email and attached my self-parsed (I'm a nerd) and raw DNA data. He got back to me before 9am! I'm a little star struck! He validated my suspicions, and is willing to talk to my doctor (Internal medicine) at the university's hospital. This is so friggin' cool, I just can't keep it to myself! Anyway, if you're into mouse studies, Google up some information on methylmalonic acidemia with homocystinuria. I'm afraid that only around 250 people are alive with my particular mechanism that branches off of that problem, but I've decided which medical school gets my corpse to train up new doctors, now! I can't be more grateful.
You sparked my interest with your personal story and the info you provided! I'm sorry to hear that you are dealing with SACD and a rare genetic complication that has caused you so many issues. But I think its amazing that you have taken the initiative to do so much research about it. Its a shame we seem to have to be our own doctors where B12 related issues are concerned, but being well informed is half the battle.
From your posts it looks as though you did the 23andme test? I considered this one, as well as ancestry, but from the enquiries I made with both companies they told me that they did not include TCN2 amongst the genes they were testing for and so I decided (possibly wrongly) that these two companies would be unlikely to provide me with answers about genetic issues effecting my B12 status. Would you recommend the 23andme test? And have your doctors shown any interest in the findings, in as far as they may effect your treatment or the possibility of other family members having issues?
I checked my results, and TCN1 and 2 were both there. It wasn't in their pretty, easy to use results, but I went and checked the genes by name and they were there with some lovely mutations in my SNPs. I swear my mom was bitten by a radioactive spider. I don't love or hate 23 and Me. I hear that Ancestry gets more raw data, but I've found enough already! It's all down to the parser that you put your raw data into. The ones that the DNA test companies use are all about huge, well proven studies. I'm willing to take the chance on studies that aren't quite as well funded. *shrug* Worked for me.
Thank you so much. It's been since 1989, so they've had awhile to test DNA against the unidentified remains that I believe to be him. Sadly, they have made absolutely no move toward doing so independent of my pressure.
I've often wondered about genetics as all 4 of my children (including identical twins) have low B12. My father had PA. My kids are too stubborn to push for treatment but one of the twins has recently had blood tests after taking oral B12 and her levels are up to 656. I wish I was a nerd like you! Thanks for sharing, very interesting 🙂
My 17 year old son tells me that it's not nice to stab syringes of B12 into family members. *sigh* Get them to look up what can happen if you don't manage a B12 deficiency right, subacute combined degeneration of the spinal cord.
My teenage daughter is currently receiving a trial of weekly B12 injections from a private GP because of various symptoms which seem B12 related.
However I worry that the frequency of injections will not be enough to provide relief to her symptoms and to therefore confirm the diagnosis. She, on the other hand, hates injections and will probably deny feeling any better even if she does feel better, just so as to avoid having to continue the injections!
So I have an interest in discovering whether there is a strong genetic component at play. She has the same TCN2 variant as me - as confirmed by the genetic test. She did have a high MMA result from a private blood test back in 2019 (which was promptly ignored by our local GP) but her level was normal at a follow up test last year (maybe due to oral supplementation).
If it stopped my kids suffering like I then I would be only too happy to stab them with a B 12 shot whether they liked it or not. There were times when I could have stabbed the little *uggers with anything. 🤺
For the interest of others -
Subacute combined degeneration is characterized by degeneration of the dorsal columns and the lateral columns of the spinal cord due to demyelination. It commonly presents with sensory deficits, paresthesia, weakness, ataxia, and gait disturbance. In severe untreated cases, it can lead to spasticity and paraplegia. 30 Aug 2021
The above reading makes you wonder why there are so many of us having to fend for our selfs ?
Mine are all over 18 now. I've tried so hard to make them see. It's an in joke with them about me now. My son even sent me a birthday card saying it must be B12 on the front. Ah well 😐
Now your what I call a cool chick - you a nerd no way. I admire your admiration which has payed off with dividends.
I have always wanted to be seen by a geneticist but unable to find one in my area. It is not I that I consider to be a nerd it is the consultants that refuse to listen or treat my symptoms.
For example. I spoke to my hematologist yesterday ( I have APs - sticky blood ) I explained my low B12 and having to inject for the last 18mnths - this was the dappy mares reply - we must do a blood test ! ! ! Please god give me strength.
I have always felt that due to the complexity of my autoimmune conditions there must be somebody within the field that would find me of interest - but this is the uk and I stand no chance of that.
I'm off to look up methylmalonic acidemia with homocystinuria. I cant even pronounce it let alone understand it but hey ho here I go to good old Google.
Sorry to hear of your dad but glad your doing your bit for science.
Heya! Thanks! If I was really cool, doctors would have listened to me and encouraged me to continue with self injecting, instead of letting me be gullible and believing them that serum B12 tests would be a good indicator that I was fine and should stop self injecting. No, the test results really were skewed by me self injecting, and yes, I really did have something like Pernicious Anemia. I needed those injections and 5mg of folic acid a day, just like the nice little old hematologist said back when I was around 15 or 16. If I had kept that up, and watched my potassium, and magnesium levels, I wouldn't have subacute combined degeneration of the spinal cord with permanent damage now. Foolish general practitioners, thinking that they knew more than a hematologist who was working before injectable cobalamin was available. I have family members who have died of this. That old hematologist had seen it all. If I hadn't ever left my hometown, and married my wonderful Canadian Army dude, I'd still have that wise old fellow's notes on my medical files. As it is, we finally got a posting to a real city and I got a doctor/professor in Internal medicine who knows her stuff. This was dumb luck and perseverance. I didn't die because I still surreptitiously injected over the counter B12 that's available here once in awhile. I should probably use those backwoods doctors, but I'm a nice Canadian and will probably just write them mean letters.
Be a pain in your doctor's butt. Keep a binder of your medical history, complete with printouts of your test results. Travel to a med school internist and get a referral to the oldest hematologist you can find. Check doctor rating sites. Tell them that you are self injecting 1cc/month of Cyanocobalamin (it keeps the best and stings the least) and take 5mg of folic acid a day. I personally take a multivitamin, 3x Cal/Mag/D3 tablets, and 2x potassium tablets a day too, with a performance enhancing L-Carnitine tablet too. I'm not talking ANY risks anymore.
I wish you all the best of luck. Find a doctor who knows what the cure for cyanide poisoning is. (Hint: 10 000 cc infusion of Cyanocobalamin)
You crease me up with laughter albeit not a laughing matter but your straight to the point attitude enlightens me.
All our good old consultants and Drs have mostly retired - drs dont doctor and our consultants rarely consult. My hematologist spent most of my consultation time apologising for being late them started discussing Margaret Thatcher - who apparently took B12 shots for a health kick !
At the end of listening to all her rubbish she was going to request another B 12 test - is she for real ? I have been injecting for 18mths.
It just shows you how ill informed these so called specialists are - this is a top leading London professor.
Do I have faith in them - NO. I will be interested in reading your next post. Take care hun.
Sadly, all I have to add is that Annie Oakley died of Pernicious Anemia, something that might shut up the consultant. Of course, their reply might be, "Who?"
The Adult Inherited Metabolic Diseases consultants who study DNA at St Thomas' Hospital in London would be interested to hear from you, I'm sure.
They were unable to find a cause for my lack of response to conventional B12 treatment frequency or for my continued raised MMA, despite revised frequent B12 injections from GP (2 injections a week). For this, they were apologetic and sympathetic, very aware they are often the last chance for a patient to get answers. I found them kind people working hard to find those answers, and who don't like giving up. If that equates to "geek", I'm glad you are one.
So methylmalonic acidemia was ruled out in my case.
They told me that, had they found a genetic cause, they would have advised my general practice surgery to administer injections at 2 a week for life. Which is exactly the frequency I was using (by this time self injecting). To their frustration, when they do have cases that shows DNA evidence to justify this frequency, patients return to them because GPs have ignored the advised frequency !
Jillymo - perhaps this is also somewhere that your GP could send you (?)
I was lucky enough to have all of my testing, appointments etc done on the NHS - except one: I once paid for a postal thyroid blood test because I wanted more results than just the TSH and FT4 that are available on NHS.
This because I have 2 sisters and now also a niece with Grave's disease, among other problems, so wanted an autoimmune picture as well. That worked out at just under £60 - at roughly £10 per test, quite good value, I thought.
I'm in Canada, so all of my appointments have been fully covered. When a doctor has prescribed the Cyanocobalamin injections, the big rubber stopped vials are around $3. DNA wise, unless a doctor deems the testing necessary you can't get it. Some provinces have a few private for profit doctors, but generally that's all plastic surgery.
The most expensive part of giving birth is the parking.
Because my doctor here was satisfied that the treatment was the same, no matter the cause, she didn't find the DNA testing necessary. I figured that it would be entertaining and keep me out of trouble, so I decided to go for it. Being able to put my DNA on GEDmatch in case my father's body was found in the USA was a bonus. The American police don't cooperate well with anyone, so just on the off chance it was worth it.
I have been to both St Thomas and Guys for my autoimmune issues and APs (sticky clotting blood). I were used for a while for research but I were never refered to geneticist or an immunologist. Infact St Thomas was where I were first seen when I were in my 20's - i'm now 70.
In the early days of my care they found me interesting. Medical science hadn't gone far enough back then to be able to diagnose. Now days they are so overloaded with patients they are reluctant to take on patients from outside of the area - infact many were discharged from clinics including myself.
With regard to their clinics - indeed your seen by the lead consultant for your first consultation then your seen by locums who come and go hense most of your consultation time is spent repeating yourself.
This so called geek has hit them all - St Toms, Guys, St Marys and the UCLH at various times for my autoimmune conditions. Where PA is concerned so long as the Dr prescribes 3 monthly injections they feel there job is done - my Gp didn't even ask me my symptoms !
It's like a post code lottery of who your seen by and if you get a diagnosis. My Gp works a two day week ! Your lucky if you get to talk to her let alone a referal.
P.s I liked you writing about ghost that is exactly how I felt - a mere shadow of my former self.
"my gp works a two day week! Your lucky if you get to talk to her let alone a referral"
This is the problem with the NHS !
No family doctor anymore, you see a different gp each time, and from experience they don't even look at the notes from the past, and start from the beginning once again.
Years ago you would of seen one G.P. who would know you, now they assume they know you which they dont and then fob you off with either medicines that do nothing or it's either to do with you life style
I also find if your refered to a consultant each one looks at a specific part your not seen as a whole person your just a part - my parts being wide spead over various parts of the country.
My thyroid and parathyroid is controlled by - endocrine
B12 - i'm to be seen by yet another neurologist next month locally the other is in London! 🎡
How many neurologists and cardiologists does a girl need ? I wouldn't mind paying toward their damned wages if I were getting answer's - but patients are being pushed round and round in circles like a load of headless chicken's. Cluck ruddy cluck. 🐔
Probs diagnose me with functional overlay - I shouldn't jest because I shall be *loody furious is he goes down that route.
It is wearing to say the least but more so frustrating because your not given answer's. ie : could the B12 issue caused my heart failure ? 💔
Who knows ? - I'm too old for this game and shall just keep taking the pills and carry on with the injections. 💉💊
Rant over - It must have been yesterdays consultation that has fired me up. 🌶😡
You don't seem like a ghost to me - can see plenty of personality in your posts and replies. Damage limitation sometimes requires you to live a smaller life than you were expecting. Or deserved. There have been costs.
You are right about lead consultants binning you off to locums on visit 2. Sometimes even handing you over during visit 1 ( rude !) However, this department was different. I was even advised to join the Pernicious Anaemia Society for support (!) and they knew of Martyn Hooper and the new research group that he is involved with - that is a lot more awareness than I have seen anywhere else, and a lot more patient-centred care.
I think key to my treatment has been my GP -who chased every lead, requested every test she could think of and spoke to experts regarding my B12 deficiency symptoms and treatment. She restarted my regime at 2 injections a week and continued this for 6 months - which was as long as it was working for me, gaining improvements gradually.
I would love to be seen by a genitist or somebody who would an interest in my antibodies - apparently I have a rare one ! I admire ButterflySugarBaby for going down that route.
I attend one of the hospitals in Oxford. In the early days my son and I were of great interest so much so they payed students to spin our blood for 18mnths - unfortunately it didn't give us answers.
My son and I both have a rare form of Hypoparathyroidism, where as my daughter like myself has the sticky blood condition Antiphospholipid Syndrome.
My Gp admits she doesn't understand my conditions and as for PA she hasn't damned clue - hence my self injecting. She works a two day week which holds everything up because your constantly waiting for her to come back on shift to read your results etc.
Where you seen in hematology at St Thomas or a different Dept ?
St Tom's and Guys work closely together. I was seen at Guys for my sticky blood condition then passed over to St Toms to one of the top hematologists. I didn't have the B12 issue back then.
Since my diagnosis of Low B12 my Dr has done very few tests yet you read of others that have had loads of tests carried out ! After a year and a half my Gp has only just carried out a MMA. I am waiting the results - maybe I shall get them next time she is in clinic !
The message on the surgery phone irritates me ( thats if your lucky enough to get through ) we will not tolerate any abuse. I think it abuse to leave the patients suffering. If i'm lucky enough to talk to her she finishes ( thats if she doesn't hang up on me ) the conversation with have a nice weekend !!! Is she being serious I can hardly walk.
I am going to do the same as ButterflySugarBaby and search the net.
I'm not well enough to travel to Londonany more but surely there must be somebody in Oxford or Bath who takes an avid interest in autoimmune diseases and genetics.
I want a Dr that *loody Drs not one that just goes through the motion and sends me around in circles which gets me nowhere. It sounds like you where lucky and hit the jack pot and received the correct treatment.
Thanks for all the information, you have cheered me up. The banter between you ladies is a tonic. I have been self injecting every ten days for many years now. It was a big battle via a haematologist to get my gp to prescribe every 3weeks. I top up privately. I was always aware that something else was amiss. On an organic acids test my MMA shows up high but not high enough for a genetic disease. It’s 3.6 and should be less than 2.3. My homocysteine is very low.. I don’t want to go to my GP about it in case a different doctor suddenly decides that once every 3 months would be ok again. I use Hydroxocobalamin.
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