- Salivary glands produce Haptocorrin (HC), which binds to the B12 in food (the extrinsic factor)
- HC/ B12 mix then travels on via oesophagus into the stomach
- HC/B12 mix can survive the low PH of stomach
- Parietal cells produce hydrochloric acid: the purpose of HC is to protect B12 from this
- Parietal cells also produce intrinsic factor (IF)
- IF has a high binding affinity for B12 but because that position is already taken by HC, the free IF and the HC/B12 empty from the stomach into the duodenum
- In duodenum, pancreatic juice (from pancreas) break HC, which frees the B12.
- Now IF can join the B12: IF/B12
- In the final part of the ileum, cubam - a receptor- recognises the IF/B12 and begins the absorption process
........well what could possibly go wrong with that ?
Well firstly, haptocorrin (HC) AKA Transcobalamin I (TC I) deficiency is seen as a rare cause of B12 deficiency, which is seen as common - although causes are not always known. This may be because HC deficiency is so rarely tested for - you can't find it if you're not looking.
Ralph Carmel did some research on this, and here are the findings:
15% (54 of 367) of those with identified cause of low B12 were found to have low HC
15% (24 of 160) of those with unexplained cause for their B12 deficiency had low HC
5% of those with malabsorptive causes for low B12 had low HC
3-5% of those with in-range B12 had low HC
3% of healthy volunteers had low HC
3 patients with low B12 has severe HC deficiency - with undetectable results
The conclusion: both mild and severe HC deficiency appear to be more common than suspected and should be considered in all patients with unexplained low serum B12
.....So, worth a spit ?
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Cherylclaire
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I'd never heard of it, despite having had saliva duct problems 2 years prior to B12 deficiency.Can't be as invasive as later functional problems - so likely also less expensive too.
I will ask the oral medicine consultant if that test can be arranged for me on next visit.
Nice summary! Such a simple process. 🤣 I recognize the name Carmel. Will reread again tomorrow with a clearer head. What is the name of the test again please, just Haptocorrin?
Sorry, I really don't know the name of the test.This is the first time I have read about it, and do not recall anyone on the forum mentioning this test before .
It could be under either Transcobalamin (TC I) or Haptocorrin (HC) ?
You can see just how many functional problems could occur - at each link, for example. Even toward the end, it could all go wonky -supposing, in the duodenum, pancreatic juices fail to break the B12 free ?
Ralph Carmel has researched B12, produced many papers and is often quoted in others.
Ok thanks. I will try to look into it. The only similar test I have found is the TC II / unsaturated binding capacity in the US, but it is meaningless to test after starting injections.
I have found a lot more research about transcobalamin II.Including a report on possible identification of susceptibility to B12 deficiency :Transcobalamin II 775G>C polymorphism and indices of vitamin B12 status in healthy older adults: Joshua W. Miller et al.
Although only 128 subjects tested, still makes for interesting reading, even if you don't get past the first introductory paragraph.
LOL nice! Maybe we should set up a shared google doc to collect this info. I have quite a few on transcobalamin deficiency and they keep identifying new variants. Not all genetic tests are able to pick up large deletions/mutations. That's separate from the SNP mutations.
I did a full genetic panel last year, everything was negative, but i did ask for a copy of the 'benign and possibly benign variants' but no reply yet.
I had 23andme done years ago and I did find a few SNP mutations, i believe in tcn 1 & 2 but i'll have to check my computer. Unfortunately they only check a subset of the possible snps. Also i really sometimes struggle to link the papers to snpedia as in, which is the bad variant - not always clear from the paper.
I'm serious about the google doc or whatever other system if you're interested
Thanks - I have had genetic testing, but not shown anything in B12 pathways; but I don’t think MCEE was analysed in mine, so am not sure if mine might be MCEE related. I think there are probably also other variants that cause disease that perhaps haven’t been identified yet.
I still have high MMA levels despite being on 3-monthly B12 injections from the GP.. I am going to try and increase injection frequency (I have been going to beauty salons for them recently!), but will bite the bullet and order some online, and will then see if that makes a difference (and brings the MMA levels down). Fingers crossed..
Sounds like it might be worth testing if you suspect it. I didn't know about MCEE & looked it up medlineplus.gov/genetics/ge...
At invitae you can get individual genes sequenced without having to do the entire panel but i'm not sure what the price difference is.
I'm guessing more frequent injections will help. SI is very easy, even if it is nerve-wracking at first. Go for it!! Definitely cheaper and easier than relying on others
I had my DNA tested by Adult Metabolic Inherited Diseases consultants. They were really my final hope after a long list of consultants. Unfortunately they did not find anything - but were very kind, said they knew I was ill but were unable to help me, to get in touch if I wanted anything checked as they hold onto your DNA sample for a few years and things change. They also went through results with me to ensure I had understood. They knew about Martyn Hooper and the upcoming research, and suggested that I join the Pernicious Anaemia Society for support. I was already a member - but it was good to come away from an appointment just feeling disappointed, but not utterly disheartened.
I am not great with computers, so don't understand about google doc or other systems - but get that it's a good idea.
But I'm still on the Oral Medicine consultant's appointment list - so hoping he has some knowledge of this HC test or is willing to have a look for it, as I have previously had salivary gland problems. Will find out next appointment I suppose.
Good thing: despite the nature of this department (eg having to examine mouth, throat, take samples for cultures) they have kept going as much as possible throughout the pandemic - including continuing training. I have had face to face appointments with students present and saliva samples taken and tested.
This must have been a high-risk procedure. Respect due for continuation of care.
Oh that's great! Very happy to hear they're on top of things despite the challenges of covid and b12 both. I assume they've ruled out things like Sjogren's?
I have come across a few.Most importantly, I have had the support of a very experienced GP.
Then, I was lucky enough to meet a senior ENT consultant who encouraged me to continue my EOD self injection routine - and warned me that it would take a long time to see results (just when I needed to know that). He also agreed with me that saliva duct strictures had a part to play in my B12 deficiency.
If I cannot find a way to have the HC test via Oral Medicine, perhaps he would know how to access it.
You are right. It is too early to say. Just expressing my own doubts.
It might not be possible to correct flaws in a system that is poorly understood and when flaws occurring later in life have unknown cause - but it may be possible to override them with sufficient/correct treatment perhaps (?)
CherylClaire! Thank you for that information. That must have taken quite a while to gather and compose in such a clear and concise way. I am going to print your summary and bring it to my doc and get some testing based on your good summary. You’re the best!
Thank you for sharing your findings, it is such a help to others. I know from my own experience just much time it can take trying to get to bottom of it all.Until recently I was unaware that the absorption process begins with saliva, I just thought thorough chewing of your food aided its breakdown in the stomach generally.
I doubt if I am alone in thinking though that the more I learn about the complexity of it all, the more I despair about ever having a sensible conversation with my my gp.
I have tried with two doctors at my practice
and one is unaware of metabolic markers like homocysteine - told me that even if she could get me tested she wouldn’t be able to interpret the results!
Oh to have such an inquiring mind! In that situation wouldn’t you think ‘this is an opportunity for me to do some research, bring my medical knowledge up to date?’
The second doctor denied the existence of an active b12 test and I know I should have pointed out that it’s been done for ages on the nhs at St Thomas’s and it is available everywhere privately but I find it really embarrassing to point such things out to someone who should know already, or at least acknowledge that there are some things they don’t know, but are willing to learn.
As with a friend who was told by a consultant that he didn’t know the answer to her question but would research the matter and tell her his findings at her next appointment.
Exactly.It would not be possible for a single GP to know everything about every condition or illness.
But they are our only access to tests and secondary care specialists.
Of the two, if those are your only choices, I would probably go for honesty - the one admitting she was unaware of a test. It opens up more of a discussion than denial that a test even exists ! Perhaps she is still able to learn something new ?
The most exciting parts of teaching for me were always when we abandoned the tried and tested -and agreed to discover "what would happen if ...." : that is where groundbreaking happens. Wonderful for future furniture makers, not perhaps to be recommended for GPs !
That's just crazy isn't it. I don't understand why doing like your friend's consultant is considered weak or bad! I've seen a number of endo's and only 1 would admit he couldn't help me, and 1 was willing to work with me, but the rest were so rigid and not interested in my unique situation.
My GP is like your friend's consultant, and despite being chased out of her office 6 years ago over an argument over B12, I still go to her... she sat and researched my hormonal issues a few weekends with one of her colleagues, I was impressed. She's a very curious person. But b12 was her breaking point I guess. One of these days when I finally have some evidence of my b12 issues, I will 'fess up that the only reason I've recovered is SI. I guess because they can't see the deficiency in labwork, they refuse to consider anything else like functional deficiency or as you say even test homocysteine/mma/holo tc/etc. That's why I ended up going the SI route, as even the neurologist dismissed all my symptoms.
Sorry for my rambling on, lots of repressed emotions there apparently 😬😂
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More curious ponderings - hypochlorhydria
Why does the cause of B12 deficiency matter?
IFAB testing guidelines per Mayo clinic laboratory website
