Hi - I'm still "battling" with Dr's and I have put all my symptoms and concerns in writing to my GP including reference to the BJH guidelines. My letter has now been passed to a Haematologist for "consideration" - it shouldn't be this hard but I'm up for the challenge as the level of ignorance and support at GP level is not acceptable.
In the meantime I have now received my 23andme test results. I have run the raw data through the "genetic genie" website (which is first class) and was hoping someone in the know could point me in the right direction for my results received for the "Methylation Profile", particularly on the following results...
MTHFR A1298C (RS1801131) GT (+/-)
MTHFR C677T (RS1801133) AG (+/-)
BHMT-08 (RS651852) TT (+/+)
What does this mean in relation to potentially being B12 deficient ? Is this relevant ?
I was also (+/-) on another x4 SNP's (?) which were MTR A2756G, MTRR A66G, MTRR A664A and BHMT-02
Any help or advise on this would be appreciated.
Thanks
A.
Written by
Ajay999
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I recall that the text that accompanies the Genetic Genie results does a good job of describing what your particular SNPs mean.
Your MTHFR mutations mean that your body isn't as good at methylating hydroxocobalamin as it should be. You should be able to get round that particular problem by supplementing with Methyl Folate (aka Metafolin) which you can get from Amazon.
The problem is that the Dr's haven't yet agreed to give me Hydroxocobalamin injections and indeed even recognising that there is anything wrong with B12 deficiency. Although I have looked at self-injecting I want the DR's to recognise the issues - after all that'e their job.
Is there any links to research etc. that i can print off that shows the link to these gene mutations and the impact they have on the methylation process ?
Ah, yes. You are anti-GPC positive,but your doctor doesn't think you have PA. While there are other, rare, conditions that will also give a positive result for those antibodies they are about 90% specific for PA - ncbi.nlm.nih.gov/pmc/articl... . Add to that the fact that you have all the symptoms of PA means that it's close to 100% certainty.
Your doc may point to the negative result for anti-IF antibodies. But that test is notoriously unreliable, giving negative results in 50% of cases where people are actually positive (see the paper above).
Your B12 levels are in the 'normal' range, but we all know how meaningless that is. Your case can be explained by the mutations in the genes MTHFR, MTR and MTRR. All code for enzymes involved in the formation of the amino acid methionine from homocysteine.
Problems with these enzymes can exacerbate a slight deficiency in B12. You may have lots of it floating around inside you, but it's not being converted to the useful methylcobalamin very efficiently.
Blood tests for methylmalonic acid (MMA) and total homocysteine should show whether the small amounts of B12 you have are working properly.
But the main thing is to get more B12 inside you. Ask your doctor what (s)he thinks is the reason behind the positive antibody test if it's not PA. Ask to be put on B12 intramuscular injections, in line with the advice in the British National Formulary (the doc will have a copy)
I wish I could show you the letter i wrote to my Doctors in December as it covered all the points you raised, i.e. BJH guidelines, asking for explaination on GPS, family history of PA etc. and asked him to put it in writing what the justification was for not following the guidelines and what the NHS position was on this subject.
I also wish my DR had the same knoweldge on the subject as you - how can this level of ignorance be acceptable at GP level ?
Re your comments..
"Your case can be explained by the mutations in the genes MTHFR, MTR and MTRR. All code for enzymes involved in the formation of the amino acid methionine from homocysteine.
Problems with these enzymes can exacerbate a slight deficiency in B12. You may have lots of it floating around inside you, but it's not being converted to the useful methylcobalamin very efficiently."
Do you have any links to research re the gene mutations and the impact these can have on the methyl processs ? THere is a lot of information available on google however i'm looking for some credible research that i can present to my GP.
It looks like a blood test for homocysteine may provide useful information. Unfortunately the test has to be carried out within 2 hours of the sample being taken. I'm hoping that this is what my haematologist has in mind for next Friday. I have to come in at 10:00 for bloods, then see the haematologist a couple of hours later.
So I've stopped my methyl folate tablets until then. I musr admit, 9 days without a jab and 6 days without my folate has got me quite knackered. Not sure what I'll be like in another 7 days.
Hi - quick question. I have been taking Methyl Folate (solgar 800mg) however I haven't been taking it sublingual. Can't you buy sublingual Methyl folate or should I be taking it sublingual for maximum benefit.
Oral should be OK. Folic acid and methyl folate are small enough to be absorbed without having to hitch a lift on a transfer protein like IF.
I also wrote to my surgery and it was passed to my GP. I listed my symptoms and quoted from BCSH guidelines (and put in the reference so the GP could look for herself) and I got a letter from the GP saying she had never heard of the treatment (the only treatment I mentioned was injections every other day until no further treatment) so she has also referred me to a haematologist and will change my treatment if the haematologist requests it only. That was Nov 12th - still not heard from the haematologist. I have asked twice at the GP about it and I get a different answer as to why I haven't heard each time. The haematologist was the one that advised her that if my symptoms did not improve after 3 weeks of injections then they are not related to my B12D She did not want to refer me to a gastroenterologist but occy health insisted on it and he was next to useless. I do wonder what was said in the referral because he did no examinations and seemed determined I was having no treatment from the get go. I did get a stool test for Crohn's but only because I suggested the test (he had said he could do a colonoscopy but didn't want to and he did not know what else he could do).
I am now waiting for my B12 to arrive by post and I am going to SI, I can't wait for health professionals to wake up. At the moment I cannot be on my feet for more than a few minutes without feeling wiped out for several days after and I start 12.5 hr shifts again next week (on my feet) and I need treatment in order to do it (I am still expecting it to be hard as the injections will not make me feel better instantly).
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I have not been tested for the MTFHR mutation - does treatment with B12 & Folic acid affect the results? Is it worth me asking for this when I go to another GP next week?
Hi - Thanks for your reply and it sounds like you are having the same issues with me (and many others) with a complete lack of understanding at local GP level, and indeed at "specialist" level.
I woudn't even ask the DR for the MTFHR mutation test as it is way above their level of knoweldge. Instead get the test done yourself, it costs £125 from 23andme.co.uk and i would defintely recommend it as it will provide more evidence to backup your case.
It's ridiculous that in this day and age people are having to diagnose themselves but as I said the complete lack of understanding at GP level is astounding.
No. The test looks at your DNA, so is totally unaffected by anything you're taking.
I'm awaiting results from 23andMe. I did get tested (for genealogy) by FTDNA, but they don't look at several of the medically-important SNPs (Single Nucleotide Polymorhisms - mutations where one DNA base is changed into another, often affecting the action of the relevant gene).
"Patients may have advanced neuropsychiatric manifestations of cobalamin deficiency and yet not be anemic, have a normal blood smear, and even have serum cobalamin levels in the normal range."
It's about gastric conditions rather than genetics but still a useful link and quote.
Forgot to mention the BHMT mutations (because my FTDNA test didn't measure them). BHMT codes for another enzyme that methylates homocysteine to methionine. It can lead to high homocysteine levels. I'm not sure if B12 is involved.
I gather that 23andMe give a fairly comprehensive report. But the site that Ajay999 used - Genetic Genie - provides a very good description of the mutations affecting methylation.
Elsewhere on the forum I wrote an explanation of the role of MTHFR and why I think taking methyl folate supplements should fix the problems it causes.
When you get your results back submit them to genetic genie. Any questions post a link to the full analysis and I'll see what I can do.
Can I ask if the 23andMe results give anything for the TCN2 gene? This is responsible for the formation of the protein that is needed to carry B12 into the cell. Mutations to TCN2 can disrupt that tranfer, resulting in high blood levels, but low levels in the cell.
If it doesn't there's a site called Promethease that will, for a small donation, hunt through the data to ascertain the presence of various health-related SNPs.
Hi Laura, the results are great and a big help for me. Follow the guidelines in the link I posted above in response to bluepettals2 and run the results through genetic genie as it will give you a report of the key genes for the methylation process - it's easy to do and really informative.
Thanks - I've just searched my genetic genie results and it doesn't seem to mention TCN2. Is it specifically mentioned in your results? It's been a few years since I ran my results through genetic genie so I suppose the information they look at may have changed.
Genetic Genie only reports on mutations in the genes associated with methylation. TCN2 codes for the protein that transfers B12 across the cell membrane, so it isn't anything to do with methylation.
If you follow Ajay999's link you'll fins a mention of Promethease This will give you loads of info on various genes - including TCN2 - Here's a screenshot of my results...
Thank you. I also got my Promethease results some time ago and can't find those but I managed to look them up on snpedia using your results. I just have CT on the rs10418 snp.
Hi - It's a bit tricky to get the reported information but if you follow the instructions on this website it should help you. Any problems please let me know...
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Does anyone know of an unflavoured brand of methylcobalamin?
Results support please
Waiting for results from a test
Couple of questions re blood results 
