Hello
I am trying to investigate low active b12 results (at the low end of the reference range). Am I better to organise a private iFab test or an MMA test? Medichecks suggested MMA but is iFab better?
My mum didn’t get diagnosed with PA with low intrinsic factor until she was very severely disabled so I am keen to do all necessary checks.
If you get a positive result for the Intrinsic Factor Antibody test ( IFAB) that is 99 % proof that you have P.A.. BUT about 50% of P.A. patients test negative , unfortunately. But that is medically recognised. A private test is quite expensive .A high result MMA test can indicate B12 deficiency. which doesn’t have to mean P.A. But if you are not vegan, strict vegetarian , are not on medication which impedes B12 absorption, are not infested with fish-tapeworm , do not abuse nitrous oxide , have not had bariatric surgery etc ( can’t remember anymore!) ,you can assume that it’s P.A.
. It’s most unfortunate that many doctors still believe that a negative IFAB test means no Pernicious Anaemia, which is not the case when you have B12 deficiency symptoms .
.i don’t think that I’ve helped you . I’ve just pointed out the pitfalls , and difficulties that we face with diagnosing P.A. There is no 100% test for the condition . It needs doctors to be aware of all the possibilities and really to act as medical detectives , which many are not . We know this to our own cost .
Thanks for your reply. My gp says she cannot order an nhs test because my active b12 was 65 which is low in the range but still within it. My blood counts are all fine. I explained my numbness and pins and needles and what happened to my mum with late PA diagnosis and she just said she would test my total b12 in 8 weeks. (That’s their common test, not active b12 which I got privately as part of a thyroid panel - I have hypothyroidism). I think I might do the mma as I have none of those other issues, and then if that shows potential for PA the gp might be more like to organise an iFab and be willing to consider my b12 as a problem.
MMA is a secondary test for B12 deficiencyIFAB is a test aimed at confirming PA as the cause of a B12 deficiency. There are other potential causes - including general absorption problems caused by variations in gut transit if you have hypothyroidism.
PA becomes more likely if your hypothyroidism is auto-immune.
Whilst active B12 is a more accurate test (repeating on the same sample gives less variation) both test are measuring the amount of B12 in your blood, not the effect of a B12 deficiency on the processes that go on in your cell. Homocysteine and MMA are secondary tests that look for evidence that cells don't have enough B12, but both can also be raised by other factors so need to be done in a context that rules out other causes of elevated levels, such as kidney problems (MMA).
Both active and serum B12 are difficult to interpret from a single point test and diagnosis of B12 deficiency is best seen from reducing levels of B12 in the blood as the body is no longer able to maintain levels at the point that is right for the individual concerned and levels start to fall over time. 65 on the active test isn't obviously indicative of a deficiency. Serum is usually 5x active so having the serum test in 8 weeks could still be useful.
That’s made it much clearer gambit62.I will definitely get an mma test to see if it adds any more information to the jigsaw. I think I have been wrongly focusing on PA because I’m scared to end up in the same situation as my mum.
My hypothyroidism is autoimmune. I have high antiglobulin antibodies but low TPO antibodies.
I suffer from silent reflux which regularly causes sore throat even when I’m not eating or drinking anything acidic, so there are definitely gut issues. I am trying to avoid omeprazole although my gps keep telling me to take it when it gets worse. I have read that most hypos have low stomach acid so it doesn’t seem like a good idea to me.
I had a celiac test years ago and it was negative. I’m not sure if that is a test result forever or if you can become celiac later in life.
Scientist, not medic. I'm just going to ramble on about results and ranges.
You say your 'active B12' is at the lower end of 'the range'. Just a thought: how was 'the range' derived? It's a minefield. The usual approach is to take a large number of samples, excluding any who are known to be on B12 supplements, and any who are known to have other pathologies such as anaemia, testing them and then analysing the results. The typical way is to calculate the mean and the standard deviation (SD), and apply (Mean +/- 2 SD) which, assuming the results obey a Gaussian distribution, will capture 95% of all the 'normal' results. So, 1 in 20 'normals' will be outside the middle 95%, but could still be normal. 99.7% of 'normals' will be within +/- 3 SD of the mean. However, B12 results don't obey a Gaussian distribution, so it's not an ideal model. Getting enough 'normal' samples is a challenge too, and performing the huge number of tests that no-one outside is paying for can be another challenge. (That's another story I'll save for another time.)
Simply adopting someone else's range isn't good practice either.
The advice from others here is valid. IFAb is a good test, but not every PA patient has detectable IFAb; only about 50% of them do, but that's got to be better than nothing. It doesn't help the IFAb negative folks however. MMA is a functional test, so in the presence of B12 deficiency, it should show a result, but it might not.
Successive FBC results might help, to see if there's any trends.
Your doctor really is the one who is central to all this, I'm afraid.
I wish there was more we could offer!
Thanks for taking the time to explain. Out of interest, which distribution does b12 follow?Also which FBC metrics should I look for a trend in? There are so many different elements.
Hi Sparkly!
B12 results, like many in nature, are skewed. It's probably closer to a log-normal distribution than a normal distribution, but it probably isn't a perfect fit. The (Mean +/- 2SD) is a crude measure but finding something better is a challenge.
As for the FBC, yes, there's plenty to watch. Fortunately, with PCs, we can spreadsheet loads of stuff. The things I'd start with are
Hb; RBC; MCV, RDW. All of those are measured directly.
MCH (which is derived from Hb/RBC) and is very sensitive.
Platelets.
Reticulocytes (when measured.)
B12
Folate
Ferritin
If you are happy with spreadsheets, then it's easy. If not, then it's a good way to learn. If your results always come from the same laboratories then that's good, because different ones may use different methods and whilst they're valid, they can give slightly different results. It's worth noting that some analytes are sensitive to delays in processing, and temperature variation too. When we see 'flyers' [results that are unexpectedly out of range, different from last time] then it's as much a matter of why that might be, and what's happened to the sample in the time from 'arm to analyser'. Likewise, was the sample a 'good venepuncture', taking slickly, and a full tube? My assumptions are all based on 'good venous samples' because fingerprick samples are even more fraught.
Good luck.
Thanks Flipper- I love a good spreadsheet so will get onto it today!🙂
That's what I like to hear! I'm sure you'll have fun.
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