Has anyone had all the bloodwork (IFA, parietal cell, MMA, homocysteine) and endoscopy & colonoscopy (including biopsies) that all came back fine yet still have B12 deficiency or PA?
Is it possible to still have PA without having any definitive test results. Endoscopy and colonoscopy did not turn up any reasons for absorption issues.
I have had all of those tests you mentioned with positive results for PA with the exception of my IF ab test was negative (false negatives are known to exist for that test). But having all negative results seem it might rule out PA with a big BUT. None of these are 100% definitive I think. It seem that during an endoscopy they would have found some evidence of AMAG but again that depends on the doctor performing the endoscopy...it quite possibly could be missed, I think, if in an early stage. I would rather focus on your symptoms. If you are having B12 deficient type symptoms...there are other questions to ask like are you vegan? if so then start with an oral vitamin B12. If you are not vegan then there are other malady's that have similar symptoms they should be testing for. This, of course, is just my layman's opinion and open for discussion.
Here’s my story: April 2020 I had COVID, about a year later I had a bizarre allergic reaction to an antibiotic. (It was induced by the sun and I felt like I had burns on my hands and feet but there was nothing visible. For several days it hurt for anything to touch my hands and feet, sheets, water, sock, etc. About a month after that I began having neuropathy in my feet and legs and it progressed to my hands and arms, also head and tongue. It was discovered that my B12 was low. Had lots of imaging done to rule out MS, aneurysm, tumor, etc. Finally saw a hematologist and neurologist. Hematologist wasn’t helpful at all but the neurologist has been amazing. In October he started me on weekly B12 injections which has helped tremendously. Still have neuropathy in my feet and occasionally legs. I just saw him and he’s moving me to injections twice a week to see if I can get more sustained relief. I also had an endoscopy and colonoscopy done last week and all that came back clear. My neurologist says he isn’t sure which of the issues has lead to my neuropathy, but either way he would treat it with B12. He’s much more about treating me and resolving my symptoms rather than figuring out the why. Which I appreciate, but just curious if we need to be exploring other possibilities or since the injections have helped does that mean it’s B12 related and all the testing doesn’t really matter if it’s come back negative. The only further test that could shed some light was my IFA. It came back at 1.0 with a range of 0.0- 1.1 being normal; however, I was on injections when that test was done.
Post covid and long covid is known to mimic b12 deficiency symptoms .Or in your case b12 found to be low
There is only so many ways the nervous system can be affected.
It has been discovered those who got very ill with covid had low b12 and vi d levels ??
So maybe the virus depletes what you have ??
so depending what you'd status was before getting the covid virus perhaps stores depleted which obviously can affect you.
So much unknown still.
Some are getting 'after effects' quite a time after recovering from covid .
Thank goodness the neurologist recognises what's helping you .
Hoping the regular b12 brings results .
I still dont know the causes but know I need regular b12.
Concentrate on getting well .
Did your neurologist do nerve function tests to find out which nerves are damaged? And did he consider the possibility of you having had a very mild case of Guillan Barre syndrome brought on by a virus which you may or may not have been aware of? It’s just one of the many things that can cause neuropathy symptoms and gets better by itself if mild.
At the first appointment he mentioned possibly doing nerve tests in the future, but when the B12 injections started and brought improvement he mentioned he didn’t think we needed to do them.
It’s been almost a year since the neuropathy started so if it was a mild case of Guillan Barre wouldn’t it have resolved by now? We did try to space injections to every two weeks but symptoms came rushing back.
The nerve conduction tests are worth doing as it tells you about which sized nerves are damaged. Whether it’s small fibre nerve damage or larger nerves in arms and legs. You have had mris to check for central nervous system damage. If the nerve conduction tests are also normal then it’s assumed to be small fibre nerve damage which is the least serious type to have. I think it’s very difficult for neurologists to be certain of a cause as there are no definitive tests for many conditions. Have you also had your Hb1ac, iron levels, thyroid hormone and vit d levels checked?
I have not had Hb1ac, but have had all the others. Although the thyroid was just TSH. My ferritin was low due to frequent, heavy periods, but after an ablation to resolve that they have slowly increased. I am being followed by a hematologist for the iron and feel good about the care I am receiving there. I just messaged with my neurologist so we will see. We are going to do three months of injections twice a week so after I see how that goes I many bring up nerve testings. He's pretty open, but also doesn't like to do unnecessary tests.
It sounds as though your neurologist is taking an interest which is hard to find. Hope all goes well.
He really is. He's amazing. He has assured me that he doesn't want me just "out there" with no one following up or taking care of me. He said he's determined to get me better.
That's good to hear. Thr NHS one I had wasn't.
Such a lottery it seems
I’m in the US. Downfall, our insurance is expensive!!! Plus side, I can see whichever doctor I want.
That’s great
I think so. The tests ard not refined enough.
Clinical diagnoses are few abd far between.
Time will tell I guess .
"Is it possible to still have PA without having any definitive test results. "
I certainly think it's possible to have B12 deficiency without any definitive test results.
In my case, I did have one below range serum B12 result but further B12 tests were well within normal range eg 300 - 500 ng/L
IFA test result was negative
Can't remember if PCA (parietal cell antibody) test was done but if it was it was negative.
Coeliac test tTG IgA test was negative, don't think other coeliac tests were done, I had already stopped eating gluten when tested and was never referred to a gastro enterologist.
I think I had over 40 different typical symptoms of B12 deficiency, possibly as many as 60 when at my worst.
Pretty sure I also had MMA, Active B12 and homocysteine tests done but I think I was already supplementing with extra B12 and these results came out normal range, I had told specialist that I was supplementing.
This flowchart from UK document BSH Cobalamin and Folate Guidelines indicates that doctors should consider continuing treatment in people who have shown clinical improvement even if tests such as MMA, Homocysteine and Active B12 show normal range results. Look on right hand side of flowchart.
Diagnostic flowchart from BSH Cobalamin and Folate Guidelines which mentions Antibody Negative PA.
stichtingb12tekort.nl/engli...
Although I think Antibody Negative PA is a possibility in my case, I also suspect that ....
1) I might be coeliac but now will never get a diagnosis as gluten has been cut from my diet
2) my B12 deficiency symptoms are caused by some rare genetic fault in how B12 is metabolised in my body
3) my b12 deficiency symptoms were caused by multiple risk factors eg gluten intolerance, viral infections, exposure to nitrous oxide during labour etc and I suffered some permanent nerve damage which is relieved by the B12 I take now.
I am aware of relatives who had symptoms consistent with B12 deficiency although no-one ever diagnosed.
What I do know is that I definitely need B12.
I deteriorate scarily fast if I stop taking it.
PAS (Pernicious Anaemia Society)
Based in Wales, UK.
pernicious-anaemia-society....
There is a helpline number that PAS members can ring.
Testing for PA
pernicious-anaemia-society....
Not sure if you can access these UK links but they may be interesting for you to read if you can.
NHS article about B12 deficiency (simply written)
It does mention functional B12 deficiency, where there is plenty of B12 in the blood but it's not getting to where it's needed in the cells.
nhs.uk/conditions/vitamin-b...
BSH Cobalamin and Folate Guidelines (UK document)
b-s-h.org.uk/guidelines/gui...
Summary of BSH Cobalamin and Folate Guidelines (main points from above document)
pernicious-anaemia-society....
BMJ B12 article
NICE CKS B12 deficiency and folate deficiency
cks.nice.org.uk/topics/anae...
There are currently new NICE guidelines in development for Pernicious Anaemia and B12 deficiency. These should be published in 2023.
nice.org.uk/guidance/indeve...
English articles from Dutch B12 website
( Difficulty of diagnosis is discussed in some of them)
stichtingb12tekort.nl/our-e...
Diagnosis and Treatment Pitfalls
(From B12 Institute in Netherlands - units, ref ranges, treatment patterns may vary from UK)
b12-institute.nl/en/diagnos...
B12 article from Mayo Clinic in US
(aimed at researchers and health professionals)
ncbi.nlm.nih.gov/pmc/articl...
Table 1 in above article is about frequent misconceptions about B12 deficiency that health professionals may have.
When I searched online for "Covid B12 deficiency" I found some interesting articles.
bmj.com/content/370/bmj.m30...
pernicious-anaemia-society....
There were several research articles as well.
My B12 was found in early 2016 to be just below range at 196 ng/L and so I was treated immediately for b12 deficiency (range started at 197 ! Phew!), low folate and ferritin which took 2 years to stabilise at good levels , osteoporosis of the spine, which has now improved to osteopenia.
My MMA was raised (GP diagnosed functional B12 deficiency which was confirmed by the laboratory) and despite frequent injections, remained so for 5 MMA tests. On the 6th and final test, 3 long years after the first, I was comfortably within the range.
Nothing else ever found: SIBO, Coeliac disease, etc ruled out. 3 months of FODMAP diet made no difference. Scans showed nothing unusual: brain, hip/groin. Nerve tests revealed nothing. DNA tests also came up with nothing.
Parietal cell, homocysteine, IFab tests all "normal". B12 obviously over 2000 ng/L, and active B12 also "normal". I have had all the tests and checks that my GP and various consultants could think of over the last 6 years.
The colonoscopy revealed a couple of polyps that were removed but not of significance. The endoscopy showed "flattened mucosal pattern" in duodenum, and "patchy gastric metaplasia" found. No explanation was given.
I have expected at times for something to show up -certainly the brain scan !- but now think that with all else eliminated, the only thing left that can explain all my symptoms is the original B12 deficiency. Despite the lack of DNA evidence to support it, I believe my GP was correct in diagnosing functional B12 deficiency -and I still self inject at the frequency she gave me on diagnosis: 2 injections a week.
Have you looked at your immediate family's medical history ? Worth it for indicators, if it is possible. My family rife with autoimmune problems: vitiligo, psoriasis, Grave's disease and yes, others have B12 deficiency too.
Over the last six years, I have managed to make gradual improvements and the only consultant still looking for answers is in oral medicine: angular cheilitis (sore, cracking, bleeding corners of mouth) and saliva gland/duct malfunction and burning tongue.
He took some bloods - thinks it is indicating vitamin deficiency !
Back to the beginning ?
After I became deficient, I was susceptible to infections that would not clear up easily and also had reactions to antibiotics, previously not experienced: specifically to Doxycycline and Metronidazole. Not as dramatic as yours- constant bad headache and vertigo.
Really glad that you have a supportive neurologist - who wisely is concentrating on gaining improvements.
It seems that my issue is a functional B12 deficiency of unknown sources. The neurologist even said at one of the appointments that the B12 is getting in my bloodstream but not at a cellular level.
I had no abnormal results from electric nerve tests to hands and feet but did not expect it - the only problems I've had with legs re nerves is two numb areas (outer shins), difficulty with walking uphill: that seemed to be a problem with brain having to work hard to make legs move, and shaking perhaps due to muscle deterioration (?) and foot-flop once only, quite late after treatment started, when I began tripping over because I suddenly could not seem to lift feet high enough to clear familiar obstacles (back door step for example) - rather disconcerting, but short-lived.
Apparently, small nerves can be tested but it is painful.
Adult Inherited Metabolic Diseases consultants can study specifics in DNA to see if they can find anything. It takes a long time and no guarantees, but they are lovely people.
They told me that their advice to GPs re patients found to have a proven functional B12 problem is administering 2 injections a week. They also told me that some patients return because GPs refuse to follow this advice !
I was lucky to have a GP who had given me 2 injections a week for 6 months, so I was already aware that this was a frequency that could help me. It certainly stopped me getting any worse, and has over time helped me make small gains towards recovery, long after expected.
I did once have a private full-panel thyroid test (because of two sisters with Grave's)- postal fingerprick testing kit sent off, test results online. Useful to rule out any autoimmune thyroid condition (anti-TPO, anti-TG) as well as checking TSH, FT3, FT4.
You might wish to push for answers by asking for an electric (large) nerve test, a small nerve test, and/or a DNA test. Be prepared not to get any useful answers after years though. They may not yet exist.
Trust your neurologist- he sounds very good.
i've had all of those tests and they came back negative. i dont believe i have pernicious anemia but I do have a b12 issue. my number was 122 when i got tested at the ER and i eat a well balanced diet. been on weekly injections ever since but my symptoms come and go, aggravated by exercise. my number has is now over 2000 but i still have symptoms of the deficiency.
Hyperchlorhydria with PA?
Colonoscopy and endoscopy 
PA testing 
State of the art testing for PA?
Possible PA
