Still seeking diagnosis for possible B12 deficiency

[pj16]

Hi everyone. I'm new on the site and am not sure if I'm on the right forum for the problems I'm having. I thought I would try as a lot of your stories I'm reading sound a lot like mine. I get very confused about B12 deficiency and blood results etc so I'd like to initially ask one question. I've just had a load of blood tests done. I believe I might be B12 deficient so what are the most important blood results I should be looking at?

[Foggyme Administrator]

Hi pj16. Not easy to answer this question because all the blood tests will be important, although some should be to do with ruling other things out rather than specifically to do with diagnosing B12 deficiency. And it also depends what tests your GP has done.

For B12 deficiency, we'd expect your GP to test, as a minimum, serum and/or active B12, full blood count (FBC), folate and ideally ferritin and vitamin D too (because those with B12 deficiency often have other absorption problems too). If PA is suspected test should include intrinsic factor (IF) antibodies.

As to ruling out other things...usual to do liver and kidney function tests, plus tests for diabetes and hyper/hypothyroidism, CRP and ESR (inflammatory markers) and routine autoantibody screen (ANA etc.).

So...all depends your medical history and how thorough your GP has been.

If you want to put up a new post with your blood test results, forum members will be able to help with interpretation. If you do so, please remember to post the reference ranges too - these are the two figures that appear in brackets after the actual result - test results are meaningless without the reference ranges 😉.

👍

P.s. You are legally entitled to ask for printed copies of all your blood results - the surgery receptionist should be able to print them out for you (some make a small administrative charge for this, but many don't) 😉

[pj16 in reply to Foggyme]

Hi Foggyme. Many thanks for your quick reply! I'll post blood results as soon as I can. In the meantime off the top of my head Serum vitamin B12 was 177 ng/L (145 - 910). Since 2015 this level has measured 400, 300, 180 and now 177. Thanks again and I'll post further results later.

[pvanderaa]

Some labs here in the USA add a caveat to results that 10 % of the population exhibit neurological symptoms when the B12 level is < 400 pg\ml.

Japan considers 500 pg\ml to be the lower limit below which treatment is required.

Start a logbook of the timing of all your symptoms. Some symptoms are interconnected in that one follows another in a fairly regular order. That order is typically due to the way your body and especially your gut works.

Monitor your food because quite often a gluten or dairy ( casein protein, not lactose) intolerance shows up with a B12D.

New, but similar, symptoms may show up when you start B12 injections or other treatments.

Stress and worry consume lots of B12 and if your gut doesn't recycle it or you have an absorption problem you become deficient in B12.

The logbook also helps with short term memory loss and sharing it with your GP may help him see the broad range of symptoms that can arise from the B12D.

Of course he may treat you like a hypochondriac at first but invite him to include a list of your symptoms, especially the nuerological ones into his record and watch his attitude change.

Good luck. You may need B12 injections before the nerve damages gets too severe and is not treated.

[pj16 in reply to pvanderaa]

Thanks to both of you for your kind replies. In the last 18 months I have had many strange (and as yet undiagnosed) symptoms. Too many to list on here and not bore you all to death but my main worries are leg pains (intermittent claudication), leg weakness/pain, tingling hands/feet, fast heart rate when walking, left sided chest pain, stomach pain etc etc! I've seen a vascular surgeon who has ruled out peripheral artery disease. I also saw a cardiologist who diagnosed moderate coronary artery disease. I am on medication for this but the cardiologist felt that he couldn't link all of my symptoms to the level of artery disease. I'm considering ordering private blood tests as all of my symptoms are having a big impact on my daily life. My GP will not test further than Serum B12. To follow up here are the rest of my blood results and I'd welcome and appreciate any comments.

September 2018

Erythrocyte sedimentation rate 5 mm/hr (2 – 16)

Serum vitamin B12 177 ng/L (145 – 910)

Serum free T4 level 10.3 pmol/L (7.0 – 17.0)

Serum TSH level 2.32 mu/L (0.20 – 4.50)

HbA1c level – IFCC standardised 31 mmol/mol (20 – 41)

Se CA 125 level 7ku/L (0 – 34)

Serum creatinine kinase level 76 iu/L (25 – 200)

Serum gamma GT level 9 iu/L (10 – 53)

Serum ALT level 15 iu/L (10 – 50)

Serum total bilirubin level 7 umol/L (0 – 21)

Serum calcium 2.41 mmol/L (2.20 – 2.60)

Serum albumin 39g/L (35 – 50)

Serum adjusted calcium conc 2.43 mmol/L (2.20 – 2.60)

Serum inorganic phosphate 1.15 mmol/L (0.80 – 1.50)

Serum alkaline phosphatase 47 iu/L (30 – 130)

Serum sodium 143 mmol/L (133 – 146)

Serum potassium 4.7 mmol/L (3.5 – 5.3)

Serum urea level 4.5mmol/L (2.5 – 7.8)

Serum creatinine 66 umol/L (50 – 100)

eGFRcreat (CKD-EPI)/1.73 m*2 90mL/min/1.73 m*2 (60 – 150)

Serum C reactive protein level 1 mg/L (0 – 7)

Rheumatoid factor 10 kiu/L (0 – 14)

Plasma fasting glucose level 4.8 mmol/L (3.5 – 6.0)

Haemoglobin estimation 129 g/L (115 – 165)

Total white cell count 4.6 10*9/L (4.0 – 11.0)

Platelet count 195 10*9/L (150 – 450)

Red blood cell (RBC) count 4.12 10*12/L (3.80 – 5.80)

Haematocrit 0.381 L/L (0.360 – 0.470)

Mean corpuscular volume (MCV) 92.6 fL (80.0 – 100.0)

Mean corpusc. haemoglobin(MCH) 31.2 pg (27.0 – 32.0)

Neutrophil count 2.58 10*9/L (1.70 – 7.50)

Lymphocyte count 1.42 10*9/L (1.00 – 4.00)

Monocyte count 0.41 10*9/L (0.20 – 0.80)

Eosinophil count 0.14 10*9/L (0.04 – 0.40)

Basophil count 0.04 10*9/L (0.00 – 0.10)

Nucleated red blood cell count 0.20 10*9/L N/A

January 2018

Serum vitamin B12 180 ng/L (145 – 910)

Serum folate 13.9 ug/L (3.0 – 20.0)

March 2017

Serum 25-Hydroxy vitamin D3 level 40.1 nmol/L N/A

Serum vitamin D2 level (less than) 10.0 nmol/L N/A

[Foggyme Administrator in reply to pj16]

Hi pj16. Oh dear...so sorry that your GP is not taking this seriously and doing their best to help you. This is something we hear here often.

First - about the blood results - although all these are within the 'normal' range, sometimes it's where results sit in the range that's important. So...

Haemocrit is towards the bottom of the range 0.381 (0.36 - 0.47) and MCH is right at the top of the range 31.2 (27.0 - 32.0). This means that your red blood cells are mainly large (macrocytic) so, more macrocytic than not. This may be indicative of a developing macrocytic anaemia - one cause of this is B12 / folate deficiency, although not all with B12 deficiency present with macrocytic anaemia because it tends to develop later in the deficiency process. So you may be heading in that direction.

Also, your B12 level is falling over time (400, 300, 180 and now 177) - evidence of an emerging B12 deficiency (the liver holds enough B12 for two - five years, so B12 deficiency often develops quite slowly s liver stores are gradually depleted).

Also - I don't see any results for ferritin (one marker of iron deficiency anaemia). If you have iron deficiency anaemia, this can mask (or partially mask) the presence of macrocytic anaemia, since the small red blood cells found in iron deficiency anaemia 'hide' the large red cells found in macrocytic anaemia. And most GPs assume that macrocytic anaemia is always present in B12 deficiency or PA - this is not the case. (And your red blood cells are showing as being very large - more macrocytic, than not).

Many GPs do not know that the serum B12 test on it's own is not a good diagnostic tool for B12 deficiency. It's entirely possible to be within the 'normal' reference range and still have B12 deficiency. So...the serum B12 test should be considered alongside the full clinical picture - and that means looking at your symptoms too. Something your GP does not appear to be doing.

Here's more about serum B12 testing:

stichtingb12tekort.nl/weten... (Problems with Serum B12 Test)

stichtingb12tekort.nl/weten... (Testing B12 During Treatment)

So...the falling B12 level over time and the 'more macrocytic than not' red blood cells do point in the direction of B12 deficiency. And you also have symptoms that are associated with B12 deficiency - including neurogical symptoms.

All the guidelines state that when neurological symptoms are present, treatment with injections should begin immediately in order to prevent the possibility of potentially irreversible neurogical damage - even if B12 levels are within the 'normal' reference range.

Here's a document that you could print for your GP to evidence this point:

archive.is/hbPHE (UKNEQAS B12 Treatment Alert, Neurological Symptoms and Risk of Subacute Combined Degeneration of the Spinal Cord – Immediate Treatment with B12 Injections)

And here are the BSCH guidelines for the diagnosis and treatment of cobalamin and folate deficiencies (what GPs should be following though many have never read them.

onlinelibrary.wiley.com/doi... (BritishStandards in Haematology (BCSH) Guidelines for the Diagnosis and Treatment of Cobalamin and and Folate Disorders). Including B12 Deficiency / PA Diagnostic Flowchart.

Also worth noting that when neurolgical symptoms are present a more intensive regime of B12 injections should be prescribed (following the loading doses, co tinge on every other day injections until no further improvement). Not many GPs are aware of this. Information about this can be found in the BNF (GP prescribing guidelines) - about third paragraph down - not many doctors read that far so,you might have to point it out. Here's a link to the BNF (your GP will have a copy on his desk):

bnf.nice.org.uk/drug/hydrox...

(BNF B12 Deficiency: Hydroxocobalamin Treatment Regimes)

Other tests that might help clarify the presence of B12 deficiency - MMA and homocysteine. MMA will be raised if you have B12 deficiency - homocysteine is more related to folate deficiency but also good to know this as you have CVD (important to reduce homocysteine if raised). (More on this in the links below). If you want to get private tests done, suggest MMA and homocysteine might clarify if B12 deficiency is present - not many GPs have access to these tests (or they've never heard of them - but worth asking).

Also - have you had IF antibodies tested (test for PA, which is more likely if a family member has PA or any other autoimmune condition). 40%-60% of those with PA test negative, so a negative test cannot rule out PA. However, worth doing because if positive, GP will have to treat you with B12 injections - for life.

To cut to the chase, the only way to know for sure if your symptoms are due to B12 deficiency (and it looks like they may be) is to treat you for it and see if this has a good clinical effect. If it does, then there's the answer and you should stay on B12 injections.

As many doctors are so ill-informed about B12 deficiency (symptoms, diagnosis and treatment) many here find that the best thing to to is become informed and collect reliable evidence to present to their GP so that they can make and evidence based appeal for treatment. Sometimes this works in a face to face consultation - often the best course is to write a 'treatment appeal ' to the GP and include evidence with a letter - when evidence is included in a letter they have to read it and it also becomes a part of your medical records - so more difficult for them to ignore 😉.

So...I'm going to paste some more inks below that will give you more information to help present your case to your GP. Lot of links in this reply and looks like a lot of reading but most are only one page long...and well worth the effort 😉. Suggest you print, read, and highlight the bits that are most relevant to your case - then use that evidence to discuss the issues - or right to your GP.

Just a couple of tips about the things you may like to focus on:

>falling levels of B12, over time

>serum B12 test an unreliable marker of B12 deficiency - can be in 'normal' limits and still have B12 deficiency. Need to also look at full clinical picture (symptoms)

>the guidelines state that if there is a discordance between test results and symptoms (i.e. test results are 'normal' but symptoms of B12 deficiency are present) then treat for B12 deficiency - most certainly if neurological symptoms are present

>symptoms - including neurological ones. All guidelines state important to treat immediately to prevent the development of potentially irreversible neurological damage (subacute degeneration of the spinal cord (though not suggesting you have this)

> 30% of those with B12 deficiency present with neurological symptoms and no macrocytic anaemia. However...

>low Haemocrit and high MCH - may be indicative of emerging macrocytic anaemia - found in the later stages of PA and / or B12 deficiency

So...here come a few more links that might help. Good luck with your GP and put up a new post if you need more help or have further questions when you've read all the information:

b12researchgroup.wordpress.... (Serious Caution Note about the use of Oral and Sublingual B12 Supplements)

stichtingb12tekort.nl/weten... (Misconceptions About B12 Deficiency – Good to Know Before Seeing GP)

stichtingb12tekort.nl/weten... (B12 Deficiency: Neurological Symptoms Can Present Even When B12 is ‘In-Range’ and Without Macrocytosis (large red blood cells) or confirmed PA Diagnosis)

stichtingb12tekort.nl/weten.... (B12 Deficiency and Intrinsic Factor – Can Be Negative and Still Have PA)

stichtingb12tekort.nl/weten... (B12 Treatment Safety / Long Term Treatment for neurological symptoms)

stichtingb12tekort.nl/weten... (Methylmalonic Acid – MMA)

cdc.gov/nchs/data/nhanes/nh... (Homocysteine Testing Information)

Good luck 👍

Ps. Forgot about gastric symptoms so...

Has your GP tested you for Heliobactor pylori - a stomach bacteria that can cause gastric issues and B12 deficeny? If not ask for a urea breath test.

Also - b12 deficiency can be caused by inflammatory bowel conditions (Coeliac or Crohn’s disease, IBS etc.). Don't see a CRP blood test. Test for so called inflammatory markers. Will not identify a specific condition but if raised, indicates that further investigations are required to identity cause of inflammation. So ask for CRP blood test.

Also - if gastric issues are a big problem, ask for a referral to a gastroenterologist - your right to do so and may help to identify what's going on.

Whatever...your GP should be mindful of your ever falling B12 level and should want to investigate further to try and identify the cause. (See the BSCH guidelines for,other potential causes of B12 deficiency 😉).

👍

[pj16]

Thanks Foggyme for taking the time to post such a detailed response. It's really appreciated. It all makes sense and I will look at the links this afternoon. I have gone ahead and ordered from Medichecks some extra blood tests - active B12, ferritin, folate and vitamin D etc. I know my symptoms get worse too when the weather gets colder and already the relentless, tingling coldness has started in my left hand and feet (UK weather). I'll consider getting MMA, homocysteine and IFA after I receive results from Medichecks. GP prescribed Omeprazole for stomach issues and I need to go back in 4 weeks to see if any symptoms have improved. I understand that she might have to tackle one issue at a time. I'm not sure about autoimmune diseases in my family but I have one sibling who has Parkinson's disease and another with plaque psoriasis. I also have vulvodynia. By the way serum C reactive protein level 1 mg/L (0 – 7) so I'm guessing that's good.

Could you or anyone else shed any light on my result for nucleated red blood cell count 0.20 10*9/L? No reference range given. Maybe this is because it's supposed to be zero?

Thanks again to everyone!

[Foggyme Administrator]

Hi again pj16. Just a couple more comments then 😉...

Parkinson’s and plaque psoriasis are both autoimmune disorders and one of the potential causes of vulvodynia is also autoimmune disease. So...having autoimmune disease in the family puts you at higher risk of also developing autoimmune conditions - like vulvodynia (incidentally, this can also be caused by nerve damage which may (or may not) also be a consequence of B12 deficiency). And Pernicious Anaemia (one of the main causes of B12 deficiency).

Here's an extract about vulvodynia.

Tests for Autoimmune Disorders

Vulvar vestibulitis syndrome and vulvodynia occur more frequently in women with two autoimmune conditions, Sjogren's Syndrome and lupus erythematosus. Fibromyalgia, which many researchers also believe is an autoimmune disease, may also be associated with vulvodynia and VVS. Your physician may suggest you be tested for these as well.

Here's a link to more information about that:

womenshealthmatters.ca/heal...

Has your GP done an antibody screen? Raised antibodies cannot diagnose specific conditions but if any of them are raised, this would indicate the potential presence of an autoimmune condition and therefore require further investigation by a rheumatologist. If your GP hasn't done antibody screening, ask for this to be done (based on your family history of autoimmune conditions - and the possibility that you also have one - the vulvodynia. And the increased potential for a PA diagnosis.

Also be aware that it's possible to have B12 deficiency (whatever the cause, PA or not) and also have an autoimmune condition - and both require simultaneous but different treatment regimes.

About the CRP - yes, a result of 1 is good (wish I could achieve that 😉). However, be aware that it is possible to have autoimmune conditions and have a normal CRP (because CRP is very reactive and can rise and fall vey quickly, depending on disease activity). And some autoimmune conditions can present with a normal CRP (i.e. when I had extremely high antibodies (ANA and c-ANCA) CRP came back as normal).

Be aware that taking PPI's (Omeprazole) can impede that absorption of vitamin B12 😖. Also be aware that if you do have PA (a potential culprit because of the links to,autoimmune disease in your family) then you will already have low stomach acid - so, if this is the case, taking omoerazole may make your gastric symptoms worse (PA causes low stomach acid and the symptoms of this are the same as the symptoms of excessive stomach acid).

Because of autoimmune history suggest you ask for anti-IF antibody test (but be aware of limitations , as mentioned above - negative cannot rule out PA (there is such a thing as antibody negative PA (AbNegPA - see BCSH guidelines in link in last reply - diagnostic flowchart).

About the nucleated red blood cells - NA means not available, in this context meaning that there is no reference range for this test.

Nucleated red blood cells are immature red blood cells that are released into the blood stream early - common causes are anaemia (iron, macrocytic - which your results are approaching - and haemolytic) or blood loss - but there are more serious and complex causes. Your result of 0.2 is very low but nevertheless, this is something that you need to discuss with your GP, who will review the result within the context of your full medical history. (I'd like to think that your GP has seen these result and would have contacted you if she/he was concerned?).

Here's what Labtest Obline day about NRBC's:

Nucleated RBCs (NRBC, normoblasts): a very immature form of RBCs seen when there is a severe demand for RBCs to be released by the bone marrow or marrow involvement by fibrosis or tumor; may be seen in severe anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers that involve the bone marrow, and in chronic low oxygen levels (hypoxemia). Nucleated RBCs can be normal in infants for a short time after birth.

Link to the full document:

labtestsonline.org/tests/bl... (Look in the section on Blood Cell Irregularities - right at the bottom).

Extract from Wikipedia:

Normally, nucleated RBCs are found only in the circulation of fetuses and newborn infants.[3] After infancy, RBCs normally only contain a nucleus during the very early stages of the cell's life, and the nucleus is ejected as a normal part of cellular differentiation before the cell is released into the bloodstream. Thus, if NRBCs are seen on an adult's peripheral blood smear, it suggests that there is a very high demand for the bone marrow to produce RBCs, and immature RBCs are being released into circulation. Possible pathologic causes include anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers involving bone marrow (myelomas, leukemias, lymphomas), and in chronic hypoxemia.[4]

I see also Martin_12 has left more information on your other post and also points out that NCRBs can also be caused by B12 deficiency (remember your 'more macrocytic than not' red blood cells, indicative of B12 deficiency - and the consistently falling serum B12 level). Incidentally, also agree with Martin's suggestion that you get MMA and homocysteine tested (as per above reply - see information about these tests in the included links 😉).

Whilst there can be serious causes for the appearance of nucleated red blood cells, please don't panic - your result is low and there are some common causes...some of which your blood test results indicate that you have. As above, this needs to be discussed with your GP and considered within the context of your full medical history 😉.

So...hope some of this gives you some idea of things to explore with your GP 😉.

Good luck pj16. Be really interested to hear how you get on 👍.

P.s. forgot to say - have you ever had a full thyroid panel - not just TSH and FT4? To get true thyroid status you would need TSH, FT3, FT4 and the thyroid antibodies TPO and Tg (to check for Hashimoto's autoimmune thyroiditis - important to check because of your and your family's autoimmune disease history). And PA and / or B12 deficiency often go hand-in-hand with Hashimoto's).

[pj16 in reply to Foggyme]

You're a star Foggyme! I wish I could write like you as you explain everything so easily. I'll examine your posts in detail tonight. I received Medichecks test kit today and am having blood drawn tomorrow. I'm desperately hoping that I can get some answers soon. The leg weakness, pain and 'growing pains' (I describe it this way because it feels like I have two different types of leg pain going on at the same time) have been really bothersome in the last few days and make me feel like I'm 75 instead of 55! Even if it turns out that I've been on the wrong forum all along I've been amazed at the help and support people offer each other on here. Many thanks.