Is 'functional B12 deficiency' present from birth?

[Gillybean1]

Hi all,

Or can it unfold later in life please?

Every best wish, G.

[wedgewood]

Vitamin B12 deficiency / PA is not well researched at all . So we can only assume certain possibilities . But if anyone of any age has functional B12 deficiency , then they will display symptoms , which are numerous and varied ,

Unfortunately, many doctors do not know anything about functional B12 deficiency which makes life more than difficult for patients . Sorry that I can’t be more helpful

[Gillybean1 in reply to wedgewood]

Hi Wedgewood,

Lovely to hear from you again ,thank you. Yes I take your point.It is odd that for an essential vitamin its not of widespread concern or interest, as eventual impact on many organs effects our healthcare systems in a more costly /time consuming way. Im not saying anything new I realise, just venting my frustration.

For me possible functional B12 deficiency its a difficult one to prove to medics. I know you self medicate and got well, you give me so much hope, thank you.

Every best wish, G.

[LWhelan]

All I know is that I didn’t start to display systems until my early 40s.

[Gillybean1 in reply to LWhelan]

Hello LWhelan,

Thank you for taking the time to reply. Yes I think it creeps up gradually up and was probably bubbling under cover very very subtly that we didnt notice.

Every best wish, G

[Catcall in reply to Gillybean1]

Hi I am 72 and I was only diagnosed a year ago !

[Gillybean1 in reply to Catcall]

Better late than never, a new lease of life i hope! G

[Gambit62 Administrator]

Functional B12 deficiency = high levels in blood but not enough getting through to cells.

There are some genetic variants that can cause this and will kick in at birth but these are rare. There are also a rare number of variants that affect how cells process B12 and may mean that a individual needs much higher levels of serum B12 but these are extremely rare.

Functional B12 deficiency is a symptom of conditions that can cause B12 to be dumped into the blood stream (liver disorders) or built up over time (kidney disorders) and this can lead to functional B12 deficiency at any time of life.

[Gillybean1 in reply to Gambit62]

Hello again Gambit,

I do wonder whether with over 20 years of supplementing with Vitamin B I have falsified my serum levels/active levels, MMA and Homocysteine. I have never had an explanation for flattened villi (coeliac ruled out), chronic gallbladder and gut pain, scalloped ridged tongue, unsuccessful hypothyroid treatment. And more recent, extremeties numb, facial spasm/numbness, toes curling under, bleeding gums etc.And a mother and maternal grandmother with PA.

I take on board what you say ,that functional B12 could be any time in our lives.

Every best wish, and thank you, G.

[Technoid in reply to Gillybean1]

paper on genetic defects in B12 metabolism :

ncbi.nlm.nih.gov/pmc/articl...

Most are quite rare indeed (or at least, have rarely been diagnosed/detected). Some are on the order of 2-3 cases ever observed.

[Gillybean1 in reply to Technoid]

Hello Technoid,

Thank you for your reply. What a paper. It will take me a long time to work through this and I am pretty sure its way over my head, but very interesting and I will have a go.

Every best wish, G

[Dilly_blue]

I have a functional B12 deficiency (diagnosed last year) and have also had low B12 levels in the past. I have been told my functional deficiency is likely genetic, and that there are an increasing number of patients being identified in adulthood.

I suspect I don’t have two faulty copies of a single B12 pathway gene (eg MMAA, MMAB, MMACHC etc etc) which would have made it much worse in infancy). I think I have had only slightly reduced B12 pathway function (maybe a single copy, or mutations in a minor - and not fully understood - gene within the wider B12 pathway, or a mutation in nearby genes that are affecting how the B12 pathway genes are expressed. For me, symptoms have ramped up and got worse in my late 40s (perhaps due to how gene expression changes as you age, or other factors in overall health that change over time).

Symptoms worsening corresponded with the menopause, for me. (I read somewhere that menopause shortens the telomeres (the protective end caps on the end of the chromosomes), which means that genes near these end caps become vulnerable to change / damage).

It is actually really really difficult here in the UK to get a diagnosis of a functional B12 deficiency, because if your B12 levels appear ‘normal’, a GP is likely to think that this rules out a B12 deficiency. I suspect getting MMA / homocysteine levels tested after a ‘normal’ B12 test hardly ever happens - I don’t think GPs can actually refer for these tests and most of them have probably never really heard of MMA / homocysteine, or understand what functional B12 deficiency is.

I suspect there are huge numbers of people who do have a functional B12 deficiency, but don’t have / can’t get a diagnosis, so my view is that a functional B12 deficiency is ‘rarely diagnosed’ rather than actually ‘rare’!!

[wedgewood in reply to Dilly_blue]

i think that you hit the nail on the head, writing that functional B12 deficiency is “rarely diagnosed “ rather than “rare”, because as we all know from reading the shocking and outrageous reports of B12 deficient / PA patients on this forum , the ignorance of the medical profession regarding the condition , is appalling .

[Gillybean1 in reply to Dilly_blue]

Hello Dilly-blue,

Thank you for taking the time to reply. How did you get your diagnosis? I am truly appreciative of having an NHS and in many many. ways we are so lucky. And here is the but...everything is 'safe' fearful of repercussions (understandably), only' this' list of meds used and' that' protocol undertaken, and if you dont fit the criteria...heaven help you.

And if you go for private healthcare sometimes that same consultant whose hands were NHS tied, unable to help, become untied and willing to trial different protocols ,such as B12 for 3-6 mths for example. I have not found that consultant in my area yet.

The gene tests are very interesting, and most likely will be used for prevention of disease in the future, currently very few medics are trained to decipher the pathways so we get shut down in conversation...not 'safe'.

I too remember reading about telomeres , age, and menopause. And I would also agree my problems started showing at perimenopause and on.

I did do MMA and Homocysteine, but scuppered the results as I could only refrain from B supplements for 2 weeks (too many symptoms exacerbated) instead of 4 months, and yes you are right GP didnt understand why I had done them, but Endocrine consultant did. With added comment we are not allowed to trial B12 here.

We must never give up. Every best wish to you, G.

[Cherylclaire Forum Support in reply to Dilly_blue]

My GP managed, on her third attempt, to get my MMA tested when I continued to worsen after B12 injections. This can be done, if you have a supportive and tenacious GP. Not easy but this effort was because she suspected functional B12 deficiency. It was diagnosed on return of a raised MMA result and confirmed by the laboratory.

How did she know that this existed as a problem ? Because ten years previously, she had had another patient struggling on B12 injections. She remembered the test required, and she remebered to eliminate renal problems as a cause of raised MMA. And she diagnosed functional B12 deficiency for the first time.

So yes, rare.

I was eventually sent to specialists who look at DNA: Adult Inherited Metabolic Diseases. They specialise in conditions that present in adulthood. Nothing could be found to explain my raised MMA. They apologised for not being able to help me. Good people. Had they found some evidence for an inherent inability to utilise B12 at cell/tissue level, they would have given me 2 injections a week for life.

This is the frequency at which I now self inject in order to control my symptoms as best I can.

I have had all the tests and consultants I could possibly ask for, and nothing else has ever been found beyond "flattened mucosa in D1 and D2" (duodenum) and "patchy gastric metaplasia". Also osteoporosis of the spine, osteopenia of the neck, low folate and ferritin, ventricular ectopics and saliva duct strictures.

By the time I got sent to the Adult Inherited Metabolic Diseases, I had already been self injecting frequently (EOD then) for six months- and finally, after 3 years and five raised MMA test results, my MMA had dropped into normal range. This proved to me that not only was it possible for my MMA to normalise, but that frequent B12 injections had eventually got me there.

That isn't to say I'm cured. It continues to be a matter of controlling existing symptoms.

[Dilly_blue in reply to Cherylclaire]

Cherylclaire - It really makes me feel hopeful to hear that your MMA levels have normalised - I hope that will be the case for me as well, eventually. The experiences I have had over the last year have made me realise that genetic investigations within the NHS are very much about confirming a suspected disorder, as I suspect this is where the maximum value lies, rather than more speculative or open-ended investigation.

I have done a lot of reading around the subject recently, and I wonder if there is a whole raft of epigenetic B12 pathway disorders which are not yet known about, and are not part of the known clinical landscape.

I read some recent research that showed that a change in a gene can affect the expression of nearby genes. I also read an article that found that dysregulation of serine metabolism was associated with Methylmalonic acidemia, (and included upregulated cystathionine beta synthase as part of this). The gene that codes for cystathionine beta synthase (CBS) is located very very close to the AIRE gene on chromosome 21 (21q22.3). I am wondering whether a single mutation on the AIRE gene (which I have) can be affecting the expression of CBS, and somehow contributing to high Methylmalonic acid levels.

Unfortunately the study of epigenetics is largely academic at the moment, not much has filtered through to clinical practice. But next time I see a consultant, I will definitely ask their opinion!

[Cherylclaire Forum Support in reply to Dilly_blue]

I wonder if it's not the Adult Inherited Metabolic Diseases consultants you should be talking/writing to ?

I think you are right: that there is an as yet unknown pathway.

I think that this team of consultants would perhaps agree.

I was told that they were unable to find the genetic source of my problem - for which they apologised. They told me they recognised that I was ill, and that my gene sample would be kept for a few years (can't remember how long now) and that if there was anything else that they could do to help, to get in touch. At the end of the line lies, at the very worst, this: respect and kindness. To be believed.

My MMA had only ever been tested after B12 loading dose was finished and maintenance injections started -and had been constantly raised, but had dropped into range on the 6th test, by the time I got sent to them, two years after the haematologist's last test. So at least I could assume that the frequent B12 injections, since nothing else was going on, were what was making the difference.

The trouble with "raised" MMA and not "high" is always that, if you wait long enough, someone will say "at your age, perhaps this is your normal ? " as normal range is apparently higher in the elderly (when exactly does "elderly" start ?) But how normal is it to have to inject EOD, then twice a week, for years and still have a raised MMA level ?

After many years, perhaps no nearer to treatment or a label, but reassuring to know that the self-treatment frequency I use through trial and error matches their advised frequency should anything of note have been found.

Interesting about nearby genes having an effect. This is something they are likely to be aware of.

On Thursday, I went to pay my respects to the Queen. It took 8 hours of non-stop queueing: standing, walking. I can still remember when I struggled to get to the local shops and back.

Keep hoping. Keep investigating.

[Gillybean1 in reply to Cherylclaire]

Oh Cherylclaire, what a journey you have had too. I am pleased and saddened at the same time, to hear yet another person who has had to push and push and push. Well done you.We have chatted before I recall, and you gave me heart then and again now.

Thank you......and every best wish ,G.

[Cherylclaire Forum Support in reply to Gillybean1]

I was lucky in that my GP was doing a lot of the pushing.

She did not give up - on blood tests, on consultants, looking for those elusive "B12 experts" to advise her.

Her reports to specialists were often commented on: I would know whether I would get somewhere or have wasted my time preparing, when a particular consultant began by either praising her thoroughness or dismissively calling them "lengthy" (aka "unread beyond Ist paragraph")

There aren't many GPs who would recognise functional B12 deficiency.

There also aren't many GPs that would instruct reluctant nurses to give a patient 2 injections a week - and continue this treatment frequency for 6 months because it was proving successful.

[Gillybean1 in reply to Cherylclaire]

Hi Cherylclaire,

At least we can be reasured that she hasnt kept this to herself in practice, and that a tiny ripple effect will be felt by some of her team/colleagues etc.

Im sure you will have seen Dr Joseph Chandy's book and body of work......someone not afraid to stick his had above the parapet and supported his patients even though criticised.

Every best wish, G.

[Dilly_blue]

I was seeing a number of different consultants (and GP) about different health issues; GP identified low B12 so I was on high dose cyanocobalamin tablets, but ended up having blood tests repeated by two different hospital consultants (different specialisms), which uncovered functional B12 deficiency. I’m now on B12 injections. Good luck with it all..

[Gillybean1 in reply to Dilly_blue]

Thank you Dilly-blue, and good luck to you too. I suspect you are onto something there re AIRE gene.

Have you read/seen The Epigenics Revolution by Nessa Carey?

Every best wish, G

[Dilly_blue]

I’ll have a look for that - sounds really interesting, thank you