I have read often that B12 in the blood stream is not important and all that is important is the B12 available at the cellular level. I have not read as of yet that it is possible to experience both PA and an inborn transcobalamin error. It seems to be a one or the other method.
With an inborn transcobalamin error the body has B12 in the blood stream but not at the cellular level. I find it rational to deduce that I am experiencing both PA and a transcobalamin deficiency
Other than a genetic test which I may investigate at a later date I find current medical treatment/diagnosis of transcobalamin deficiency to be even less credible/effective than the current treatment/diagnosis of B12 deficiency .
I have found very little information about the treatment for transcobalamin. It is rarely diagnosed and therefore considered to be rare. Most often diagnosed in infants. Likely as that is the only time that genetic test is performed and then only rarely tested.
What little I can find about treatment of transcobalamin is administration of large amounts of B12 and 'various' forms of B12. Which I find rational.
I went over my many trials of different trials of forms, methods of administrations and amounts of B12. I noticed that every change in form was followed by a marked improvement followed by a leveling off. The sum of which was overall improvement over time. I deduce this is the result of using different forms of B12 over time.
At one time I administered methylcobalamin/adenasolcobalamin SL at the same time as SC in an attempt to administer more B12 and that has been the most appropriate treatment for what I experience.
We are all different and if hydroxocobalamin IM 1 mg every other day and symptoms will stop improving is adequate that is great. I choose to try and find what was different about me and how to treat that differently. It does help that the most current and robust protocol is not as much about science as a negotiation with those in authority to be allowed to inject at all. See Dr. Chandy's very valuable work with the UK government agencies.
I am injecting .50 mg SC of hydroxocobalamin three times a day and administering 5 mg of methylcobalamin/adenasolcobalamin SL three times a day.
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WIZARD6787
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My symptoms are substantially reducing. I went with more is better which it was. I will now work out if more is not necessary now I take three different forms.
congrats wizard!! I would do exercise and get depleted rest a week, up my doses and exercise again. Now I exercise a lot and can kee up if I I ject twice a day.
Good on you. I often wonder if frequency is part of the puzzle. I will be able to open water swim in the USA in a month. It makes me cry to feel like I will again be able to do a mile a day if I want. We shall see. I have so many hikes I think I will be able to do again! One of the first severe symptoms was I would get hypothermia no mater what the temperature of the water. That was 2 years 9 months ago.
"Lately it occurs to me. What a long strange trip it's been." Grateful Dead
It was both frequency of the doses which sped up the recovery from 2 years to probably never if I had not upped the frequency. And then also my liver needing time to get the stores built back up enough. Both frequency and time are required for a more timely recovery in my case and as I've seen many others. I kept trying to space injections only to regress.
Thank you for that!!!!!! Right now it feels like I have no storage and I work with that assumption although medical science has not allowed that is possible. I would say yet but I have no faith it will ever happen.
Genetics is, strictly speaking off topic for this forum.
Genetic disorders affecting the production of transcobolamin are rare and will manifest quite early in life - generally in infancy.
There are a few other very rare genetic variants that affect the efficiency with which B12 is used in cells.
Nobody, to my knowledge, really understands why some people who have had injections report needing to maintain much higher levels of serum B12 to function properly - and there are a number of competing theories.
Is it common to believe that Transcobalamin deficiency is always fatal at birth if not treated and therefore does not exist in anyone alive that did not receive treatment?
Its caused by a specific set of variants on a specific gene that controls the production of the protein transcobolamin. Having one of these specific variants will mean that the protein doesn't get created properly so no B12 gets into cells - which would result in death because vital processes won't run. I think it usually manifests within the first few months though the full effects may take a couple of years to lead to death
Thank you for your reply. Your efforts are appreciated! Transcobolamin Deficiency is no longer considered fatal and the term used is Late Onset of Transcobolamin Deficiency. It is still considered rare although I allow that the diagnosis is complex and likely to be missed.
The treatment for Late Onset of Transcobolamin is not unlike the treatment for PA with regards to B12. Difference is 1mg is administered per day to start and recovery is complete within a year. Alleviation of symptoms is 4 to 6 weeks.
"After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated."
I have come across Betaine as a treatment in many places. It seems to be about Homocysteine.
It is a minefield to be sure and does not lend itself to checkbox thinking.
For me personally after 2 years 5 months from diagnosis I have a solution that is effective unless I have an unexpected setback.
I use "Simply Spectrum" instead of the typical B complex as it does have all the B vitamins along with what is used to treat Late Onset of Transcobolamin Deficiency. The only thing it does no contain is Betaine.
The two loose end I have right now are why I need B6 which is definitive that I do need it and the note in the chart from B12.org that says with Transcobolamin II "Various types of cobalamin may be necessary."
To be clear I am not saying I have Late Onset of Transcobolamin Deficiency, that I have not been tested for. It is interesting that what I came up with with critical thinking to self treat happens to match.
According to this paper from last year there have been only 150 recorded cases of adult-onset transcobalamin deficiency : ojrd.biomedcentral.com/arti...
Yes, but is this because it's not being considered and diagnosed rather than because it barely exists?
How does one get tested for transcobalamin deficiency, partial or otherwise, and how does one get tested for transcobalamin antibodies? Is anyone looking at these things?
Clearly those of us who need very frequent injections, have some issue with B12 transport into the cells and are having to swim in B12 just so that some of it gets where it is needed. But of course, there is no issue and we are just malingering and are making up our need for B12!
Thank you for that. I needed it this morning. I was questioning whether I really needed more B12. Fact is I do need more than B12 then is known by most experts. Most probable cause is transolaman deficiency.
"Yes, but is this because it's not being considered and diagnosed rather than because it barely exists?"
I think the same argument could be made for any rare disease. It could be rare because its not being looked at or considered by physicians. But it could also be rare because... its genuinely rare. Without a lot of widespread genetic testing its hard to say whats the case either way.
"How does one get tested for transcobalamin deficiency, partial or otherwise, and how does one get tested for transcobalamin antibodies? Is anyone looking at these things?"
Outside of specialist private testing or participation in rare medical studies, very unlikely to happen. I find it hard enough to get my GP to even run a normal run-of-the-mill blood panel let alone anything more esoteric... I appreciated the link to the article describing partial TC-II deficiency of which I was unaware.
"Clearly those of us who need very frequent injections, have some issue with B12 transport into the cells and are having to swim in B12 just so that some of it gets where it is needed. But of course, there is no issue and we are just malingering and are making up our need for B12!"
Its very clear to me and every other forum member that many PA and B12 deficient folks need B12 injections more often than makes any sense from the point of view of most B12-related blood measurements (with the exception of those who have a raised MMA, which does clearly indicate a medically confirmed issue with B12 getting where its needed). I have no idea why this is and I'm pretty sure nobody else on this forum does either. There is simply not enough current research on the subject to say either way.
Could it be that there are large amounts of undiagnosed patients who have partial TC-II deficiency? It's possible but we really have no idea since the proper research on that still needs to happen.
I'm not sure if this was directed to me but I'm certainly not suggesting that anyone here is "malingering" or "making up their need for B12". I'm just not fully convinced by the hypothesis that this need is caused by undiagnosed TC-2 deficiency, or antibodies to TC-2. I think the whole phenomenon needs a lot better research attention and although we can speculate on possible causes based on current research I don't think conclusive explanations are available for it yet.
We know that the enteropatic recycling system does not work normally in the case of PA so this may be part of, but not the full picture.
In the USA I am close to many medical research facilities and have friends that work at some of them as well as one friend who works at Rush University medical school. When I get back I will tell them I want to be part of a study. I am not gong to pay $450 to have the genetic test done.
Thing is I would not change my self treatment no matter what the test said. Reality is the medical personnel I work with would not adjust their thinking anyway. My body behaves like it has no storage capacity for B12. If I 'use it up' for whatever reason I suffer. If I treat my body as if it has no storage capacity it is easier to be me.
Taking it easy in hopes I will improve later does not appeal to me and no one is sure that will be effective. More B12 more often is effective for me.
It is credible that if some people need my B12 than others something is different. Something is unknown but it is definitively different. Allowing for 'doing well' is subjective. Being in pain is relative. I am in more pain if I do not self treat assuming I have no storage capacity.
Thanks for the reply, totally agree with what you are saying and apologies for my less than scientific statements.
And yes, when I mentioned people assuming patients are making up their need for B12, it was not directed at you, but pointing to the response of some medical professionals who many people in this forum have struggled with. Sorry if it came across directed at you! Definitely not.🌷
Thank you for the information it is appreciated. Maybe with autopsies someone could do a report about how many people died from it due to failure to diagnose.
This is a 'very rare disorder' which would come under rare diseases. If it were something any of us on the forum had inherited without treatment I dont feel we would have survived to adulthood.
Also, what is more likely in our cases: the production of transcobalamin antibodies in response to the injections. There are a few studies from the 70s noting this. sciencedirect.com/science/a...
It's a shame that we are not being investigated for these things.
"Furthermore, nothing indicated a hampered distribution of cobalamin from the plasma pool during the weeks after injection of hydroxocobalamin or other untoward effects ascribable to an increased production of antibody to TC II."
If I read this correctly it appears that the antibodies did not seem to cause any issue with B12 takeup to cells. The reasons why this would be so are not clearly explained that I can see.
Thanks for doing that. Although you make me look lazy.😀
Does seem counter intuitive.
I had no idea what an antibody was. "An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects."
Kinda makes sense the the body might increase antibodys given the chance with more B12.
I am more and more in awe how critical the neurological system is. Less and less about medical personal who seem to "Try and hide what they don't know to begin with." Bob Dylan.
Very helpful discussion for me. In this moment I am going with the standard view of B12 which was amazing 25 years ago is outdated. I do not want the results of 25 year old understanding.
A huge obstacle to those that have current understanding is the political restriction of one mg of hydroxocabalamin every other day for either Intrinsic Factor issues or Transcobalamin issues being the extent of treatment allowed. (Not related to genetic testing.)
I know of one physician who shall remain nameless to protect their career who is prescribing .50 mg of Hydroxocabalamin every day and 5 mg of oral methylcobalamin every day. That is the best they can do. It is not the best I can do.
The link to a video, below is about B12 in general. I do not know who made the video. In the video she goes over the standard second tier of testing and mentions it is to diagnose issues with Transcobalamin. Again the current treatment is the same. She also states that 25 % of B12 patients have Transcobalamin issues. (Not related to genetic testing.). That % does not include those not diagnosed.
She does not go into details like 40% false negative of Intrinsic factor tests etc. Which as a scientist I understand is reasonable in a short general video.
The link below is to the British Committee for Standards for Hematology's Guidelines for the diagnosis and treatment of cobalamin and folate disorders. It does include the chart referenced in the video. It is dated 2014 and I do not know if it is current.
She mentions in the video that the National Formulary recognizes Functional B12 deficiency as a Transcobalamin issue. I have not found that documentation. This is not my country and I am not familiar with the various bureaucratic entities.
The only different course of action I am taking based on this discussion and my new reading is I am going to try a trial of Betaine which is mentioned several times by those that treat Transcobalamin Deficency.
My current self treatment is:
.50 mg SC Hydroxocobalamin3 times a day.
3 mg SL Methylcobalamin/Adenosylcobalamin 66.6%/33.3% 3 times a day. (Mailed to me from USA.)
.25 mg Pyridoxal-5-Phosphate liquid in water twice a day.
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