Pernicious Anaemia Society
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High serum B12, High Active B12, Anaemia, Elevated Liver Enzymes (ALP & GGT)

Hi everyone, I'm posting for first time.

My son (22yrs old) is autistic, with dysmyelination (abnormal/lack of myelin). He has had high serum b12 levels (ranging between 1116ng/L to >1500 ng/L) since 2007. Liver enzymes have always been high (in particular Alkaline Phosphatase and GGT. RBC, Haemoglobin and Haematocrit .

He is not on any vitamin b12 supplements and his diet is restricted. He takes high doses of vitamin b6 in the form of pyridoxal-5-phosphate to control seizures.

I am worried that the B12 is this high, despite no supplements and in light of his myelin situation (which i understand is connected to vitamin b12) what could be going on? He has been anaemic for a number of years despite iron supplements. He has always been very lethargic prior to the anaemia and since he was born.

Is anyone able to shed any light, ideas on what any of this means please?

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gmouton.com/img/fichier_55a...

You might find this of interest. Certain variations of small intestine bacteria overgrowth can result in raised b12 levels and can be resolved by adjusting the diet.

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Thank you so much Steap :) This is very helpful and I will include this with my letter to the Gastroenterologist and GP.

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beyonddisease.com/sibo-and-...

This work suggests a link between SIBO and raised liver enzymes.

It's also suggests that probiotics can play a role in helping to reduce the raised liver enzymes.

There are of course many theories floating about there but it does seem plausible that gut dysbuosis could be contributing to at least some of the issues you raise.

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My son is planned to have an Gastroscopy on 15th March under general anaesthetic so I can use this article to see what the Gastroenterologist thinks.

I note that one of the SIBO tests is a jejunal aspirate which would be brilliant if it could be done whilst under this scope, though I think the endoscopy only goes as far as the duodenum. Unfortunately my son would be unable to do the hydrogen breath test which I think is the only other test I've come across.

Thank you so much for this info.

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it may be a genetic problem with metabolising folate and B12 rather than directly related to diet. Liver problems can also raise B12 levels.

Possible that he may have a functional B12 deficiency - MMA and Homocysteine will be raised if this is the case.

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Yes, it could be genetic. I brought this up with the neurologist in January, he said he'd look into the genetic side of things and will get my son onto the NHS "genome project", but I know that this will be a stretched out process (and we still not heard from him!). So in the meantime, I thought of looking at any other possible causes.

We've done the urine MMA test and the Homocysteine through the GP, but don't have results yet. However, I think Homocysteine may not be accurate as my son is on very high doses of vitamin B6 which I think is involved in bringing Homocysteine down (?!)

Thanks for your reply.

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the process that recycles homocysteine uses B6, B9 and B12. I suspect that high B6 isn't actually going to affect the usefulness of the test as all 3 are needed - aware that it becomes a difficult test to interpret if B9 (folate) is low as it isn't clear which of B12 and B9 is causing the problem but if B9 is high then it becomes more straightforward.

B12 deficiency causes a different type of anaemia from iron deficiency.

Generally high levels of B12 aren't a problem - though elevated levels can be an early indicator of other problems (eg liver and kidney). In some people elevated levels of B12 in serum can cause an auto-immune reaction which stops the B12 getting from blood to the cells where it is actually needed - functional B12 deficiency - but you'd need to look at his symptoms but the symptoms do overlap with iron based anaemia and a lot of other conditions.

Hope that you manage to get a resolution soon.

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Thank you for the explanation.

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It sounds like your son may have Methylcobalamin Synthesis Deficiency: CblE (OMIM 236270) or CblG (OMIM 250940) Disease. There have been several published studies that show direct correlation between high liver enzymes and B12 in patients with this synthesis deficiency. It is possible that your son's liver is unable to uptake the cobalamin (B12) to convert it to an active form of B12 (methylcobalamin). This would do three things: 1) it would cause pernicious anemia since red blood cells mature by using B12 in its active form (methylcobalamin). 2) It would also cause a high serum B12, since the liver isn't uptaking enough/any. 3) It would cause an unhealthy increase in homocysteine (which can act as a demyelinating nerve toxin). This is because Methylcobalamin (B12) is needed by methionine synthase to convert HCY into methionine.

Below I have attached the symptoms/clinical finding of this disease (which correlate with your description of your son) as well as the current treatment. I have also attached a link to the publication that I referenced for this information. Best of luck to you and your son!

Clinical Findings

1.

Most patients become ill within the first 2 years of life, but a number have been diagnosed in adulthood.

2.

Megaloblastic anemia.

3.

Various neurological deficits including developmental delay, cerebral atrophy, EEG abnormalities, nystagmus, hypotonia, hypertonia, seizures, blindness and ataxia.

4.

Failure to thrive.

Treatment

Hydroxocobalamin administered systemically, daily at first, then once or twice weekly. Usually this corrects the anemia and the metabolic abnormalities. Betaine supplementation may be helpful to reduce the homocysteine further. The neurological findings are more difficult to reverse once established, particularly in CblG disease.

sciencedirect.com/topics/bi...

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Hi Lab-Lady,

Thank you so much for your response and the link. My son fits all the clinical findings you have listed except for the megaloblastic anaemia. His anaemia so I am told by the GP, is iron deficiency anaemia.

However, when my son was 7yrs we did a couple of months of methylcobalamin injections, I am not sure if at all, having given him these and also DMG/TMG it would have corrected or changed these metabolic abnormalities somewhat??. He also had high homocysteine at the time and we started giving him Methyl-folate, Vit B6 (P5P). With recent labs his Homocysteine was within range and Activie B12 was high.

I will have a look at the two Methylcobalamin Synthesis Diseases you have mentioned.

Once again thank you for your input, much appreciated.

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Has your son ever been tested for thalassaemia? It is possible for such a trait to hide and coexist with a megaloblastic anemia. Anyhow, I really hope that this forum at least helps you narrow down some possibilities so that your son can receive effective treatment. As far as your question concerning whether the methylcobalamin injections and DMG/TMG changed the metabolic abnormalities: it really depends on what he has, but it is not likely. If one of the methylcobalamin synthesis diseases is present, then the metabolic abnormality is permanent, however consistent treatment may mitigate the symptoms. In any case, the question becomes, did your child seem to improve with those treatments? Any difference? (less seizures etc?)

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