I was diagnosed with a 'functional vitB12 deficiency' last year (I had high levels of MMA (methylmalonic acid) in my blood, but normal vitB12 levels in my blood as I had been taking max prescribed dose of cyanocobalamin) - which essentially means that although I have vitB12 in my blood, my body can't actually use or transport it, so I am 'functionally' deficient) - does anyone else have this, or know anything about it?
I have lots of symptoms, some neurological and quite a lot of muscle weakness, and I started treatment (from GP) with hydroxocobalamin injections in December / Jan (I had the loading dose of 6 injections). My symptoms came back after 5 weeks. I had an injection last week after a gap of three months, and my symptoms were back after 4-5 days. I'm not sure what I should do now. I tried to ask my GP for more frequent injections a month ago; he sent me for a blood test to check B12 levels (GPs can't authorise MMA tests apparently; I had previous one at a hospital) - but I tried to tell the GP that it would most likely be normal (as I am 'functionally' deficient), but he insisted on the test anyway.
I think I need to see a specialist in functional B12 deficiencies, as I don't think my GP understands what it is - I suspect that most typical haematologists don't know much about it either (I know a hospital haematologist socially, who didn't really know much about it). Can anybody recommend someone?
Many thanks in advance
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Dilly_blue
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I’m so sorry to read what you are experiencing. Unfortunately, we cannot recommend anyone and vitamin b12/PA is commonly misunderstood. You do get the odd amazing doctors. (A private GP said I bet you know more than me and I was honestly thrilled).
Other members will be along soon to go through processes as to how to get better treatment and lists of organisations.
Me, personally, I wasn’t going to waste my energy arguing with doctors. I know my body best, keeping a diary of symptoms. A simple tick chart/table or there are apps. I self inject as do many of us.
Yes with functional B12, you don’t know what’s going on at cellular level so that B12 blood test after treatment had started is totally useless - in my humble opinion. But backed by the British Haematology Society.
Thanks so much for your reply. The functional b12 deficiency diagnosis was a bit of an incidental one - I have been having ongoing investigations for a potential muscle / connective tissue disorder, and they screened b12, MMA and homocysteine, and I got a diagnosis, very much in a 'oh by the way...' kind of way. I am not sure what to do, but seems like self-injecting may be my best option going forward if no joy from GP.
Aside from neurological symptoms (tingling feet, tinnitus, double vision and periods of dizziness) I have quite a lot of muscle problems.. my hands are very weak when I wake up (I can't make a fist) which takes a while to settle, I have shoulder muscle problems, and I think my breathing muscles are also affected (I have rem-related sleep apnoea and I am on C-Pap at night - but noticed that my breathing was much much better for about 5 days after my last injection).
I also have problems with my ankle and wrist tendons shortening (my fingers are getting increasingly deformed / bent) and to be honest, I am wondering whether this is all b12-related???
I tore a tendon in my ankle. I have been searching research articles for a connection between B12 and tendons but haven't found anything. I am very interested in seeing people talk about it here!
Thanks for this, WiscGuy - I find it all very interesting how B12 is often linked with so many other issues / disorders. I think the dots really need joining - I suspect it may be an underlying causal factor in a lot of things..
I noticed at one point that my hands were weak. I especially noticed it when shaking hands. And they were a little puffy and stiff when I woke up in the morning. My doctor initially followed the regimen for hematologic symptoms (a week of loading doses, then an injection every ice age or two; my symptoms improved, then returned, worse. After a few months I said I wanted to go to daily injections, and my doctor grumbled but didn't fight me, and the hand things have totally resolved.
Thanks - that sounds exactly like me (I can’t pick up pillows when I first wake as I can’t bring my finger tips to touch my palm so I have much less grip strength) but it gradually wears off over a few hours. It’s great that it is under control for you now
Thanks so much for your messages.. I can't tell you just how much it means to have someone say that they have experienced the same thing!
I have seen some very very experienced neurologists, and rheumatologists, and they all drew a complete blank about my tendon problems....
Unfortunately the neurologist who diagnosed my functional B12 deficiency did it via letter after he had discharged me from his clinic (the MMA result was delayed), so I have no way of consulting him now..
I have been almost crippled for months now, I did have a knee injury years ago, been fine for about 25 / 30 years then last year started to cause problems, in January ankle on other foot started to cause really bad pain, then out of nowhere my knee popped, you know that pain when your mouth opens but no scream comes out. Had injection in knee which has helped a bit but my ankle, tendon is noticeably swollen at back of heel, and crippling. I am self injecting every other day, hoping it isn't permanent.
That sounds like the tendon that is giving me trouble: peroneal tendon. It comes down on the outside of the foot, just behind the ankle, and goes under the heel, where it splits into the peroneal brevis and peroneal longus. I tore the longus. (I have complicating factors: very wide feet, and very high arch, called"cavus", which puts added pressure on the tendon. I babied it all winter, and in the spring, when the swelling had gone way, I got orthotics, which both cushion the heel and support the high arch.)
I have just recently bought some really comfortable indoor shoes with a bit of a heel (and am looking for some heel raises/lifts to go in my outdoor shoes) - I am finding if I avoid walking about with my feet flat on the floor (ie no walking barefoot or in flat shoes at all) then that really helps my tendons in my ankles.
I was finding that if I spend a lot of time in flat shoes or barefoot then it is agonising in the back of my ankles, really throbbing and painful (like someone has just hit you there with a baseball bat). I am assuming that it is because flat on the floor requires the tendons to be at maximum stretch, where they don’t really want to be any more. I am about a week into my new regime with my heeled indoor shoes and it has massively reduced the pain and hobbling!
What you are doing sounds very much like what the doctor advised me to do: walk as little as possible; and wear shoes (with closed heels) rather than sandals, flip-flops, etc. I also had a touch of plantar fasciitis, and when that didn't clear up he gave me a shot of steroids.
WiscGuy - You don’t mind me asking if you by any chance get stiffness in your back/ neck and/or pelvis that starts in the early hours of the morning, or generally after resting and gradually eases up with movement, or back problems generally? I have ankylosing spondylitis as well (plantar fasciitis is a common symptom of that), and back/neck/pelvic stiffness and pain are also common symptoms of that. I have recently wondered whether there is a link between B12 issues and ankylosing spondylitis, as both seem to run in my family..I know it is unlikely, but I thought I’d ask!!
You are on the right track. As you might know, absorption of B12 in the digestive tract requires intrinsic factor, which is produced by the parietal cells, which are in the wall of the stomach. Often (I guess not always) in B12 deficiency, the immune system attacks the parietal cells, or the intrinsic factor, and without intrinsic factor a person can't absorb B12 through the intestinal tract, and so B12 deficiency is often considered to be an autoimmune disorder. Rheumatoid disorders, such as ankelosing spondelitis, are also autoimmune disorders, and there are many others, such as colitis, psoriasis, and on and on. A person with an autoimmune disorder is generally considered to be at risk for other autoimmune disorders. And, as you mentioned, autoimmune disorders run in families. They run in my family, but so far I am the only one with B12 deficiency.
Thanks for your message - I’ve found it can be very difficult unpicking which symptoms might be due to each condition, and I think my doctors have found that too!
I’m really sorry to hear that - and hope it will improve for you. I’ve found that there is a very large lack of information (or understanding) about what some of the neuromuscular symptoms might be, occasionally there is almost an afterthought of ‘and muscle weakness’ in the list of symptoms, but no sense of what these might be and what the long term impact of them might be. I am having big problems with employment due to muscle issues - and this seems not to be recognised in the literature at all, unfortunately..
I had the trigger finger problem last year. A steroid injection sorted that out. I can still type and play my piano.Often it is better to leave the GP out of the loop and do it yourself with Hydroxocobalamin injections. I am on a five day cycle at the moment. My peripheral neuropathy, sensor nerves) is controlled with gabapentin. My GP knows about the frequent injections but cannot support it. He will support the pain meds though.
Thanks for your reply. It’s good news that you got your hand problem sorted out
I suspect something like a 5 day cycle might suit me too - I felt so healthy and mobile (and positive) a few hours after the first of my three-monthly injections last week, (had loading dose over Christmas period) but all of the symptoms came crashing back within 5 days, and I now feel really upset about the whole situation.
From looking at all of the other threads in the forum, it is so striking at how many people are massively affected by this (major debilitating symptoms coupled with an inability to get adequate treatment in the UK) - it is a complete blind spot in the medical landscape, I think...
Sorry to hear this Dilly_blue .Sorry also that this is a very long story that many here have heard before, but it might help you:
I was first diagnosed with functional B12 deficiency by my GP because I was found to be B12 deficient (just under the range) - but did not respond to loading dose (6 injections, over 4 weeks) and deteriorated rapidly on "maintenance" dose of 1 every 3 months.
She had my MMA tested. Not easy - she was refused by several hospital laboratories but persisted. As she suspected, my MMA was raised, even though my blood was now swimming in B12 (over measurable amount of 2000ng/L). She gave me a diagnosis of functional B12 deficiency, confirmed by the laboratory.
There are other causes for raised MMA: renal problems had already been ruled out as a cause, later small intestine bacterial overgrowth (SIBO) also ruled out by breath tests. SIBO bacteria can rob host of vitamins- including B12.
The reason she knew what to do was because she had had one other patient with the same response 10 years earlier -and this was the diagnosis eventually arrived at. This is incredible doctoring and I was extremely lucky. It is unusual and not well understood.
I was given two injections a week. About three months into this frequent treatment regime, I felt the injection for the very first time ! It didn't hurt at all, but I felt something. I kept improving, so the regime continued. Everyone could see it was working: GP, nurses, friends and family.
Then I got worse again - and injections got reduced to 1 a month. Not good. This was the "....until no more improvement can be had" part, when you get moved on to the maintenance dose of a generous monthly jab. But I was deteriorating, so was sent to consultants.
Most of the consultants that I saw had very little understanding of B12 deficiency and none of functional B12 deficiency.
Haematologists tried warning me off by saying that B12 was toxic, carcinogenic, highly addictive. I just wanted to stop getting worse again. I asked for proof three times, some research, anything - of course there was none given, as none exists. Frustrating, insulting.
I showed them the only research I had on Functional Vitamin B12 Deficiency (M R Turner, K Talbot, 2009) - the only response from locum was "but look at the date" - this was in 2017 !
Despite these dire warnings, they continued to test my MMA levels: always raised. They sent me to neurologist, electric nerve testing, brain MRI, SIBO breath test. Nothing found. They decided that raised MMA was my "normal". They told my GP that my treatment frequency should certainly not exceed the guidelines of 1 every 2 months.
This was when I came to the conclusion that I was only going to deteriorate again on this frequency, that the GP would not go against advice that she had requested and that I was likely to lose my job if I could not get a phased return started very soon. I began self injecting and told my GP at an appointment the day after I started (in case she tried to talk me out of it - which she didn't anyway). The frequency I chose was every other day injections initially.
I saw many consultants - while most were against what I was doing, no alternative cause or treatment was ever offered, and one delightful ENT senior consultant told me on inspecting my mouth that B12 deficiency was evident, that I was doing exactly the right thing, to keep on self-injecting and not to get disheartened -it would take a very long time.
And it has !
Now, seven years after first going to my GP, I can say that I am much improved, still get disheartened when not so good, but able to finally believe that most symptoms are gone, reduced or very rare. I still know that they can quickly return and I am only keeping them at bay by frequent self-injecting, now at twice a week. Not a cure, but a way to get a life back. My life.
Your answer could be different.
I suggest you read the Turner and Talbot report and make your own mind up about functional B12 deficiency. It is not wonderful: my copy has a large advert for tablets while the report suggests that "such patients may respond to repeated high-dose injections of B12." It's something though, and it might help you.
This might help more though: I did see consultants from Adult Inherited Metabolic Diseases, who looked at my DNA for reasons for my raised MMA but could not find anything that would help. They are able to advise GPs to administer B12 injections twice a week if they find a functional problem in DNA. Some surgeries still refuse to do this even then, much to their frustration, and these poor patients have to return to them.
Ignorance is not bliss for some, is it ?
I did eventually give up on my phased return to full-time work though, and took voluntary redundancy during lockdown. I felt I'd given it everything I could and only ever managed two days a week at best. Sometimes at worst, too.
Get folate, ferritin, vitamin D and thyroid checked regularly, rather pointless checking B12 in blood though. My folate and ferritin levels were low and unstable for a couple of years, my vitamin D3 is now on prescription as part of effective treatment for osteoporosis of the spine. Folate and ferritin now seem stable and at optimum levels without supplements, even osteoporosis reduced now to osteopenia - but this took 2/3 years. Even my 6th and final MMA test was finally down to within range after 3 years.
All of the above tests, monitoring, GP and consultant appointments (and many others) were done by the NHS. I once had a private full-panel thyroid test to include autoimmune checks since there are many problems of this nature in my family. This is not available on the NHS to my knowledge.
You are right: functional B12 deficiency will raise MMA despite a lot of B12 in the bloodstream because the link is not able to be made well between them, and so B12 does not easily reach tissue/cell level.
It seems logical then that if more B12 is introduced, more might make that link and get further along the process. But I'm not a scientist. I'm an ex-teacher, and an ex-woodworker. Not yet sure what I'm going to be next !
Thanks so much for taking the time to send such a detailed reply - it is much appreciated and has made me feel more hopeful. I’m glad that things have been improving for you since your diagnosis.
I am very interested in finding out more about the Adult Metabolic consultants that you saw - I might look into that as an option to perhaps get more information. Is there a guideline somewhere that says that if there is an inherited cause (DNA mutation) found for functional b12 deficiency then you are entitled to twice a week injections? I would be really interested to find out more about that.
I’m not sure what the future holds for me (re: employment) either- I think a lot depends on how it all goes over the next few months. I think if I have a distinct ration of productive time in the day, then it will be very important to find something very fulfilling!
You may find this, about genetic B12 metabolism disorders, of interest. This seems to be my family's underlying problem, with PA a late stage diagnosis. ncbi.nlm.nih.gov/pmc/articl...
Thanks so much for this.. it is incredibly interesting. From all of the reading I have done so far, I was wondering whether there was a more chronic / cumulative type of inherited B12 pathway disorder (sort of like a baby cousin to methylmalonic acidemia). I have found my health started deteriorating in my 30s and from my late 40s has just accelerated (tests last year showed a small amount of gastric parietal cell antibodies and ANA, but low enough levels to not prompt further investigation). I have also had gastritis for about 10 years, so I have a suspicion that I am gradually becoming more unable to absorb (in addition to having a functional deficiency diagnosis).
I suspect that a functional deficiency gradually damages your intestines, to the extent that the amount you can absorb reduces (and I presume ends up as a PA diagnosis). I read a statistic (from a research report) somewhere that had taken a cohort of people with PA and run tests, and they found that (from memory) quite a significant number of them also had a functional deficiency. I think it was something like 30 percent (but I may have remembered that number completely wrong! - it may be something like 7 percent - sorry! My memory has been really atrocious for the last few months..!). If I can remember where the article was I will try and post it (if I can work out how).
Bookish - have your family ever had the exact genetic mutation diagnosed? How have those affected in your family been diagnosed with functional b12 deficiency? It strikes me as incredibly difficult to get a diagnosis - as GPs don’t tend to know about MMA and homocysteine tests (or they are not available for them to order, which is the case around here) so no-one will ever know what is going on at the cellular level..
My diagnosis was a bit of a fluke to be honest.. (and arose because I had a period where I was seeing a number of different hospital consultants at the same time. I am wondering how to get my kids (and wider family, siblings and parents) screened for MMA and B12?
Sadly I am having the same issues as you say re. diagnosis. In the family all we get is a PA diagnosis or nothing. My Dad's GP is uninterested thus far and I am imminently going to run it past my neurologist, if I can get my brain into gear, as rheum dismissed the idea three years ago (which was partly what prompted me to do a limited genetic test). My understanding is that in adult onset we are often talking epigenetic changes, SNPs, rather than mutation and new papers are coming thick and fast suggesting different areas of likely genetic hiccups re B12 metabolism, which isn't yet well understood. This paper talks of 8, but I have other papers talking of others. The point is that there are good reasons for further investigation beyond 'serum fine hence patient wrong'. I've only had two of these eight tested, and one was fine, one wasn't (MTR, cblG). I've just done my first reading of Dr Chandy's 'Vitamin B12 Deficiency in Clinical Practice' (but have had covid since, so have forgotten most of it and need to begin again!) and he suggests (I think) that the lack of needed B12 and folate results in the DNA methylation and epigenetic changes which then predispose us to higher vulnerability to our weaknesses - like autoimmunity and PA. So if you can treat the deficiency early enough, in some at least the PA may not develop. And that is my plan!! I am 5th of 6 generations, the oldest 3 all having had PA but of course no B12 given until obvious symptoms. Dad and I and youngest family member are all self treating and have been for years as we knew there was an issue, just not what and why. Now we may have an idea why. (I have other folate/ B12/methylation SNPs, not just MTR, don't think it is as simple as just one SNP and bang).
You'd have hoped that your having even low level parietal cell antibodies would have been investigated as it will likely affect your production of stomach acid and therefore digestion and nutrient absorption, as well as affecting your intrinsic factor production. So iron, B12, anything tricky to absorb. Even if it is only a sign to monitor, it is surely significant. There are private tests available, but I haven't tried any of them. Best wishes
Thanks for your message. I was trying to get blood tests (B12, MMA and homocysteine) for my parents privately earlier in the year - there is a lab (linked to an NHS hospital) that does them (and you can get a mobile phlebotomist to take the bloods and send it in the post I think), so I contacted them, but they said that they weren't offering those tests at the moment (I suspect they were probably focusing entirely on the covid effort at the time - sequencing covid strains and other tests etc).
I might try and contact them again to see if they now offer those tests privately, for my parents. If so, and if results show that serum B12 is low, and MMA high, then I think a re-test after 2-3 months on the max dose of cyanocobalamin (tablets, not hydroxocobalamin injections, as hydroxocobalamin will normalise the MMA and completely hide the fact that there is a functional problem) will highlight a functional B12 deficiency if there is one (as the serum B12 will then be normal (due to the cyanocobalamin), but the MMA will still be high (as I think cyanocobalamin can't be accessed at the cellular level if you have a functional deficiency).
Unfortunately the lab doesn't do tests for under-18s. So I may have to also seek a private hospital appointment to get my kids screened, as my GP can't get MMA tests done at all (even if he were willing to humour me), and without MMA results it is impossible to rule in (or out) a functional B12 diagnosis - so frustrating
Interesting points. I understood that B12 metabolism issues could mean serum B12 was high, never mind normal, even without supplementation. And as I have supplemented for years, looks like I'm unlikely to get a useful result from MMA or Hcy. Best of luck with your testing.
Thanks.. Yes, b12 serum results can also be normal or high in functional deficiency, it is actually the MMA level (or homocysteine level) being high that signifies.
I think if b12 serum level normal or high, while MMA high then that means functional deficiency straight away.
The difficulty comes when b12 serum level is low (and MMA high, or not tested), as it will be assumed to be a nutritional deficiency, and only treated with tablets for a few months (as with me).
So by re-testing after a few months of cyanocobalamin tablets, this will highlight a functional deficiency (which was also what happened to me - as a hosp doctor requested tests). Although - homocysteine does respond to cyanocobalamin, so homocysteine levels may look normal when re-tested, when there is actually a problem).
I am not sure how long the effects of hydroxocobalamin last - I suppose it must depend on the individual (I got my symptoms back after 5 days after my last injection (last week), so it must mean that MMA levels are building back up in my body. Maybe leaving off the injections for up to 3 months (as is typical on the NHS) if your health permits, would enable you to get MMA and homocysteine tested and see what is going on?
The other way round, I know it takes only up to a week or two for MMA levels to normalise / significantly improve after treatment (as I read up on it to see whether my MMA levels remaining high after 3 months of cyanocobalamin were due to how long it takes to have an effect, but it wasn’t)...
Thanks for that. I don't inject and symptoms worsen very quickly without oral/sublingual plus methylfolate (which actually made more difference for me). Will have to see what neuro thinks. I came off everything for rheum and he refused to do any testing and I can't afford more private tests as have already spent a fortune to get as well as I am now x
That sounds like a really difficult situation to be in, so sorry to hear that. Do you have the typical neurological symptoms - tingling extremities, tinnitus, double vision or glare issues (see halos and starburst lines around lights at night time) etc? I suspect these are taken more seriously as a cause for testing as they can become irreversible.
Your neurologist should have access to MMA and homocysteine tests; I think given your substantial family history of PA, and genetics findings then they should definitely investigate further (and it is shocking if they don’t).
I think sometimes consultants specialise a lot in a very small and defined area, and I suspect that one can’t rely on them to know a huge amount about anything that sits outside their particular sub/micro-specialism, unfortunately...
I have emailed Viapath Nutris (the direct-to-patient blood testing service / lab based at St Thomas’ Hosp in London; they have a range of tests, which include B12, MMA and homocysteine) to enquire for my parents, I will report back if I hear anything..
Thank you so much for all this useful information! I am still pondering over the different types of B12 affecting MMA and Hcy differently, which I hadn't heard before. Do you suppose that will vary depending on where the particular functional problem is? I took cyano for (many) years, in small multivitamin types doses, then in larger more absorbable sublingual doses, which helped a bit, then changed to methyl, helped some more, then a better methylcobalamin plus methylfolate and big improvements. Just added some adenosyl. All the usual tingling, burning, pins and needles, hypersensitivity weirdness, fatigue, vitiligo, restless legs, palpitations etc for years, then added increasing numbness and vertigo so neuro diagnosed small fibre neuropathy and I have fibro, so possible Sjogren's, but with thyroid and B12 issues so strong in the family I suspect they are playing a bigger role. I do get odd flashing lights usually in the dark, often when leaving early for work, so will run that past him too, thanks. No tinnitus or double vision. Vertigo stopped with methylfolate, vitiligo stopped increasing with anti-inflammatory auto-immune diet. Gluten a problem for me and neuro said that all of my issues could be gluten-related, but that was before I knew about the genetic B12 stuff.... Cheers
I’ve just tried to find the study that said Hcy affected by cyanocobalamon, but MMA not, but I haven’t found it! Instead I found a study that said they were both reduced by cyanocobalamin (in older patients). So probably best to ignore my previous message as the facts are questionable.. sorry! Literally dropping on my feet now, so need to sleep!
Hi, I'm finding this whole topic fascinating - I'm a few months into my journey and unless I've misunderstood what you've written need to correct you. I've had 2 MMA tests, the first after 5 x B12 hydroxocobalamin injections within 3 monthsof the 1st test - 3 weekly prior to the test. I continued with weekly injections and had a 2nd MMA test after another 4 injections and my results had got significantly worse. My understanding of this is that my functional B12 is worse. I've just had a very poor experience with a haematologist but am now going back to the neurologist. I was initially diagnosed with folate and B12 deficiency because of severe migraines, but when I started taking folic acid I started getting tingling in my hands and feet and a very sore mouth - the tingling has not gone away but the intensity and the state of my mouth seem to be pretty good indicators of what's going on - the haematologist told me to stop weekly injections but has now said (and written to my GP) that I can have them for 3 months, for me that just buys me 3 months to try and find another solution eg, why has my MMA increased even on weekly injections, get the other causes ruled out........... I expect like many others I will resort to more frequent injecting until I find the right frequency as weekly isn't it. In laymans terms I think when I started folic acid (I stopped it very quickly) it stripped any functional B12 that I did have and because I process B12 so inefficiently I can't catch up - any advice welcome
Hi Avins - sorry to hear it is all so problematic. I am not medically trained - and have only been reading up on things in earnest for around 5-6 months (after being diagnosed functionally B12 deficient last year), but I think if it was me (with rising MMA despite Hydroxycobalamin injections) I would push for a fairly urgent Adult Inherited Metabolic Disorders referral asap, to rule out an adult-onset inherited disorder.
I think there is a massive blind spot in the medical profession as a whole - there seems to be a fair amount of knowledge about inherited B12 disorders with 2 copies of a faulty gene (Methylmalonic Acidemia / Aciduria & Homocysteinuria etc), as these tend to occur in the first year or so of life, are very severe, and have two copies of whichever faulty gene is causing it (I think there are a number of genes and polymorphisms that have been found so far). B12 injections may help some of these but not all (there are other treatments for those not responsive to B12). These disorders are very much in the province of Inherited Metabolic Disorder specialists / departments. (Orphanet suggests prevalence of 1-9/100,000, for Methylmalonic Academia (which roughly translated means 'abnormally high levels of methylmalonic acid in the blood'. 'Aciduria', is in the urine)).
But there seems to be very little known about inherited B12 disorders that are milder, become mainly symptomatic in adulthood, and maybe only have one copy of a faulty gene (an article I read recently identified that there were only 45 examples (patients identified) of this in the literature. Being a lay-person, and in simple terms, to me it seems statistically much more likely to 'throw a six' for a single dice, than for a pair of dice together (in terms of inheriting either a single copy of a faulty gene or two copies of the faulty gene), probability 1 in 6 for single dice and 1 in 36 for both, so I imagine there could be at least 100 to 300 times more people with a milder version (and a single copy of a faulty B12 pathway gene), than those with a severe version (two copies)??? ps- Apologies if my understanding of these things is not that great..
I think it is potentially a massive black hole, or blind spot in the medical landscape - a small proportion of those will get a diagnosis of 'functional B12 disorder', but I imagine that the majority of people with a mild (one faulty copy of a B12 pathway gene) disorder, will not get a diagnosis, as MMA or Homocysteine is usually not tested alongside B12, so it is impossible to differentiate between an inherited or functional deficiency, and a nutritional one - and serum B12 may not actually be abnormal anyway. Part of me wonders whether there are a multitude of people with an unknown single faulty B12 pathway gene being treated for a host of different health conditions across all parts of the health service, all caused by the underlying, hidden, B12 issue???
Some references below (if I have managed to attach them correctly, technology not my strong suit!).
Avins - the diagnostic flowchart may be helpful to show your neurologist, and see if they will refer you on to an Adult Metabolic Inherited Disorder Clinic?
Cause of and diagnostic approach to Methylmalonic Acidurias.. High MMA – diagnostic flowchart on page 354, table listing causes page 355 (Journal of Inherited Metabolic Disorders 2008)
Thank you for taking the time to reply, I will look into all of those links and go prepared - the neurologist that I've been seeing has been very thorough and I'm hopeful that he will refer me on.
Only just spotted this, and just wondered if you were actually taking folic or folate. If your genetic metabolic hiccups are similar to mine, you might get a better response with a methylfolate (methyltetrahydrofolate - I use Metabolics liquid (metabolics.com/methyltetrah..., then I can use as much or as little as I want) instead of folic acid. If you try it, please start slowly, but it made a huge difference to me. I started with just one drop and now take two or three, three times a day a that seemed to suit me best. Best wishes
I am also very interested in the genetics / epigenetics side of things. I think it is all so complex and inter-related.. I read that high MMA levels in the body have a cascade effect on the expression of roughly 300 other genes (epigenetically up-regulating some and down-regulating others). It's scary to think how much of an impact this could have in the body, and how little is known about B12 deficiency.
There seems to be a big gap in knowledge - between what is known about the severe / acute metabolic B12 disorders that appear in infancy (like methylmalonic acidemia), and nutritional B12 deficiencies and autoimmune pernicious anaemia.
There is a big grey area in between those, which probably includes chronic metabolic B12 disorders, inborn partial / autosomal dominant deficiencies, which (if identified - which is unlikely as it seems impossible to get MMA tested) just get termed 'functional B12 deficiency' - no follow-up, no clear understanding of what the actual problem is, or what it might lead to (or is actively contributing to), or how to treat it effectively. Or how to stop it being a problem for the next generation. Rant over, sorry everyone!
Thanks for your message. I am really interested in finding out more about that - eg whether a Biotin deficiency a nutritional issue/deficiency, or is it produced by the body? (And if so, is it likely to be an inherited issue?) I am at the stage where I want to find out as much as possible, especially if there are other things (alongside B12 injections) that might help matters!
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