Links to info: Active-B12, or holo-transcobalamin,

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Links to info: Active-B12, or holo-transcobalamin,

Postby anotherwithpa » Sat Jan 05, 2008 5:00 am

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Active-B12 or holotranscobalamin (HoloTC)

Postby anotherwithpa » Fri Feb 27, 2009 4:00 pm

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Postby anotherwithpa » Tue Jun 23, 2009 7:59 am

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Axis Shield

Postby bethanpasoc » Fri Jul 31, 2009 5:57 pm

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Active B12

Postby anotherwithpa » Sat Aug 01, 2009 7:03 am

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Postby kimks mom » Wed Aug 05, 2009 9:23 pm

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PostPosted: Wed Aug 05, 2009 10:56:am Post subject: Holotranscobalamin test may be superior to B12 test
from PubMed


[The role of holotranscobalamin in examination of vitamin B12 status]
[Article in Serbian]

Cabarkapa V, Stosić Z, Uzurov V, Sakac V, Derić M.

Klinicki centar Vojvodine, Novi Sad Institut za laboratorijsku medicinu. veliborcabarkapa@nspoint.net

INTRODUCTION: Holotranscobalamin contains biologically available cobalamin because only holotranscobalamin promotes the uptake of the cobalamin therein by all cells, via specific receptors. Therefore holotranscobalamin has been proposed as a potentially useful alternative indicator of vitamin B12 status. The aim of the present study was to assess usefulness of holotranscobalamin in the evaluation of vitamin B12 status. MATERIAL AND METHODS: We examined serum level of holotranscobalamin in 135 subjects divided in four groups according to the serum concentration of vitamin B12: 30 subjects with vitamin B12 <154>350 pmol/l. RESULTS: The results show that in subjects with low vitamin B12 serum level there are those with normal holotranscobalamin concentration (60%) and that in subjects with normal vitamin B12 there are those with low holotranscobalamin concentration (22%). The obtained results also show positive significant correlation between levels of holotranscobalamin and vitamin B12 (r = 0.62, p < -0.001). CONCLUSION: We can conclude that biologically active cobalamin, holotranscobalamin, is a useful tool when examining vitamin B12 status especially in subjects with borderline and low vitamin B12 concentrations. Measurements of the serum holotranscobalamin may be superior to total serum cobalamin.


PMID: 19097377 [PubMed - indexed for MEDLINE]



http://www.tinyurl.com.au/x.php?1wr

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kimks mom
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PostPosted: Wed Aug 05, 2009 3:59:pm Post subject:
Hi Jane,

The holotranscobalamin test is the active B12 test that some of our members from your country and New Zealand have had done.

http://www.active-b12.com/active-b12-in ... ve-b12.php

In a comparison between the serum B12 test and the active B12 test, a friend explained it to me in this way:

"However, as you should now appreciate, the current bunch of serum tests do not test for B12; they test for B12 bound to transcobalaminII (the real thing) and simultaneously for B12 analogues bound to haptocorrin (dross), without differentiating between the two. It's particularly unfortunate that 60-70% of the stuff in any given sample is bound to be dross."

Hopefully, the active B12 test will replace the serum B12 test universally perhaps with a push from the PAS.

Regards,
Pat
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I don't have PA. I am a support person for my daughter who does have PA.

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PostPosted: Wed Aug 05, 2009 6:54:pm Post subject:
It realy would help if people tried to keep to already existing topics, this would fit in here:
http://www.pernicious-anaemia-society.o ... hp?t=10060

What I understand from the dutch forum (holo Tc is now tested in several hospitals in holland) that the problem is that the values for "normal" are constantly alterring, and again different hospitals use different values for "normal".

Testing for holo trans II is done in Schotland, Mo had it tested, not privately either.
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I'm no medic, just have PA and can only try to understand, offer support and learn from my own and other's experiences.
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I am a support person for my daughter who was diagnosed with PA and Folate Anaemia in 1994, at the age of 27. Another daughter diagnosed with Hashimotos 2010 but she doesn't have PA.
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Postby anotherwithpa » Fri Aug 28, 2009 10:04 am

Info from dutch forum:

13 augustus 2009
Diagnosis of vitamin B12 deficiency: a new Active-B12 EIA

The prevalence of vitamin B12 deficiency in the general population is greater than previously thought;
early diagnosis is crucial because of the possible risk of irreversible neurological damage.
The widely used total serum B12 assay, however, does not reliably indicate vitamin B12 status.
To improve the accuracy of diagnosis, the concept of measuring holotranscobalamin (Active B12) has aroused great interest.
This article introduces newer methods for Active B12 measurement, explores the issues and discusses the clinical utility of Active B12.
by E. Valente


Vitamin B12 deficiency
Vitamin B12 deficiency is widespread and a major public health issue..
Among the population groups at risk are the elderly, pregnant women and their offspring, vegetarians and patients with intestinal diseases.
The classic haematological signs and symptoms may be absent or non-specific.
Neurological symptoms may be the only manifestation of deficiency and can be irreversible if treatment is delayed.
Early and accurate detection of vitamin B12 deficiency is therefore important.

The current widely used analyte, total serum B12, is now recognised as being a late marker, with sub-optimal sensitivity and specificity.
The diagnostic challenge associated with this has lead to the search for earlier and more accurate biochemical markers for vitamin B12 deficiency.
Holotranscobalamin, or Active-B12, has been shown to be an early marker of vitamin B12 deficiency and may fulfill this role.

Active-B12 (holotranscobalamin)
Intrinsic Factor (IF), transcobalamin (TC) and haptocorrin (HC) are three binding proteins involved in the assimilation and transport of vitamin B12.
These binding proteins ensure the efficient uptake of the very small amounts of dietary vitamin B12.
All of these proteins have extremely high affinity for vitamin B12. with dissociation constants around 5fM [1].
When transcobalamin and haptocorrin bind vitamin B12 the resulting complexes are known as holotranscobalamin (Active-B12 or holoTC) and holohaptocorrin (holoHC).

The function of transcobalamin is to transport vitamin B12 from its site of absorption in the ileum to tissues and cells that express specific receptors.
The vitamin is then internalised as the Active-B12 (holoTC) complex.
Once in the cell vitamin B12 is an important co-factor for two enzymes.
As adenosyl cobalamin it catalyses the formation of succinyl-CoA from methylmalonyl-CoA; methyl cobalamin is the co-factor for the conversion of homocysteine to methionine by methionine synthase.

Circulating vitamin B12
Normally, less than 30% of the vitamin B12 in plasma circulates as Active-B12 (holoTC). The remaining ~70% is bound to haptocorrin, whose function is uncertain.
It is thought that haptocorrin transports surplus B12 to the liver and may also be involved in clearing B12 analogues (corrinoids) from the circulation [2].
Absent or dysfunctional haptocorrin is relatively rare, clinically benign and usually discovered accidentally [3].
On the other hand, absent or dysfunctional transcobalamin manifests as the typical haematological and neurological pathologies of vitamin B12 deficiency [4].
This condition is usually discovered shortly after birth and aggressive therapy is required to avoid irreversible neurological damage.
Frequently, in such cases serum analysis shows misleading total vitamin B12 levels (within the normal range).

Diagnosis of vitamin B12 deficiency
Accurate assays for determining vitamin B12 status are needed because of the high prevalence and serious complications of deficiency.
Typically, vitamin B12 deficiency is suspected only when an individual presents with haematological manifestations of megaloblastic anaemia, which tends to occur only in the most severely vitamin B12 depleted individuals [5].

Determination of total plasma vitamin B12 concentration is the current standard clinical test for vitamin B12 deficiency.
Depending on the method and population under investigation, total vitamin B12 concentrations of less than ~150pmol/L (200pg/mL) are generally considered indicative of deficiency.
However, a proportion of individuals with vitamin B12 levels that would be considered deficient exhibit no clinical or biochemical evidence of deficiency [6].
Conversely, neuropsychiatric and metabolic abnormalities can occur with plasma vitamin B12 concentrations well within the normal reference range [6,7].

Limitations of total vitamin B12 assays
The measurement of total plasma vitamin B12 suffers from a number of limitations, most particularly that the majority of vitamin B12 that is measured is the fraction bound to haptocorrin.
As Active-B12 (holoTC) has a shorter circulating half-life compared to holohaptocorrin, the earliest change that occurs on entering negative vitamin B12 balance is very likely to be a decrease in plasma Active -B12 (holoTC) concentration [8].

Total vitamin B12 assay indeterminate zone
There are many publications attesting to a significant indeterminate zone when using the total vitamin B12 assay.
Around 30-40% of all requested B12 determinations would fall within an indeterminate zone of 151-300pmol/L.

It has been estimated that vitamin B12 deficiency can occur up to total B12 levels of 300pmol/L and even beyond, and that 45% of vitamin B12 deficient subjects would remain undiagnosed if screening only measured vitamin B12 level [9].

This suggests an initial clinical utility for Active-B12 (holoTC) in order to resolve indeterminate vitamin B12 results.
It is expected however that Active-B12 (holoTC) will eventually supplant total serum B12 as the initial diagnostic test for suspected vitamin B12 deficiency and may also have utility for screening.

Measuring Active-B12 (holoTC)
The use of Active-B12 (holoTC) as an accurate marker of vitamin B12 status was first proposed by Herzlich and Herbert in 1988 [8].
The cloning of the transcobalamin gene paved the way for new assay methods based on specific transcobalamin antibodies [10,11].

Very recently a novel monoclonal antibody was developed with at least 100-fold specificity for Active-B12 (holoTC) as compared to transcobalamin apo-protein (TC), which has allowed the development of simple, direct immunoassays for the quantitation of Active-B12 (holoTC) [12,13].
Such assays avoid the need for the various reduction/extraction/conversion steps employed by most vitamin B12 assays, thus removing a possible cause of pre-analytical variability.
Axis-Shield have been in the vanguard in developing methods for estimating Active B12, having developed the first EIA on the Abbott AxSYM analyser and having further automated methods in development.
Additionally, there will soon be a new microwell EIA, available from Axis-Shield.

The clinical utility of Active-B12
As expected, Active-B12 (HoloTC) levels are low in patients with biochemical signs of vitamin B12 deficiency [14]. Low values have been reported in vegetarians [15,16], vegans [17], and populations with a low in-take of vitamin B12 [18].

Some comments regarding the use of Active B12 are quoted below:
• “HoloTC can be used as a first line parameter in detecting cobalamin deficiencyâ€
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Functional vitamin B12 deficiency.

Postby anotherwithpa » Sun Oct 18, 2009 9:28 am

Functional vitamin B12 deficiency.



Pract Neurol. 2009 Feb;9(1):37-41. Links
Functional vitamin B12 deficiency.Turner MR, Talbot K.
Department of Neurology, John Radcliffe Hospital, University of Oxford, Oxford, UK.

We describe a case of functional vitamin B12 deficiency where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2. Such patients may respond to repeated high-dose injections of B12.

PMID: 19151237 [PubMed - indexed for MEDLINE]

Some more info in this topic:
http://www.pernicious-anaemia-society.o ... hp?t=11132
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AXIS-SHIELD GRANTED US PATENT FOR ACTIVE-B12 TEST

Postby anotherwithpa » Sun Jan 17, 2010 12:10 pm

http://www.axis-shield.com/index.cfm?ac ... newsid=234

AXIS-SHIELD GRANTED US PATENT FOR ACTIVE-B12 TEST
12/01/10
Dundee, Scotland, 12 January 2010: Axis-Shield (LSE:ASD, OSE:ASD), the international in vitro diagnostics company, today announces that is has been granted a US patent for its technology governing the specific detection of Active-B12, or holo-transcobalamin (holoTC), as a more effective way of determining vitamin B12 deficiency. The newly granted patent lasts until 2024.
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Determination of serum holotranscobalamin concentrations.

Postby anotherwithpa » Tue Feb 09, 2010 10:52 am

Determination of serum holotranscobalamin concentrations with the AxSYM active B(12) assay: cut-off point evaluation in the clinical laboratory.



Conclusions: Our results confirmed the analytical reliability of the AxSYM HoloTC assay. The method is adequate for routine use and a cut-off threshold of 40 pmol/L is appropriate for assessing cobalamin deficiency in populations with reduced tB(12) values. Clin Chem Lab Med 2010;48:249-53.
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Determination of serum holotranscobalamin concentrations

Postby anotherwithpa » Tue Jul 06, 2010 8:44 am

Whole 5 page PDF :

Determination of serum holotranscobalamin concentrations with the AxSYM active B(12) assay: cut-off point evaluation in the clinical laboratory.

http://edoc.hu-berlin.de/oa/degruyter/cclm.2010.032.pdf
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Postby kimks mom » Tue Dec 28, 2010 1:50 am

The active B12 web-site has been updated...a lot of information on it regarding B12 deficiency; diagnosis, absorption and lab tests:

http://www.active-b12.com/

I am marking this with a sticky so the information provided on the web-site is easily accessible.
I am a support person for my daughter who was diagnosed with PA and Folate Anaemia in 1994, at the age of 27. Another daughter diagnosed with Hashimotos 2010 but she doesn't have PA.
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Postby martyn » Tue Dec 28, 2010 8:17 am

Well done Pat - interesting to see us as number one in the links section!
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Postby Diesel » Fri Jan 14, 2011 9:36 pm

My tells you more about Vit.B12 deficiency

Vit.B12 Hydroxo-cobalamin injection dependant 1995 Sublingual Methyl-cobalamin and Adenosyl-cobalamin tabl. 2008

True knowledge exists in knowing that you know nothing
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Postby martyn » Sun Jan 16, 2011 8:16 am

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