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Holotranscobalamin – An Early Marker for Laboratory Diagnosis of Vitamin B
12
Deficiency
and normal holoTC.
15
A combination of a low concentration of holoTC Table 1: Population Groups at Risk of
and an elevated MMA was found in approximately 16% of the elderly
Vitamin B
12
Deficiency
subjects; this represents subjects with a metabolic sign suggesting
cobalamin deficiency.
15 Group Causes/Comments
Vegetarians, vegans Low intake of vitamin B
12
and macrobiotic diet
Taken together, available functional biomarkers such as MMA and
Neonates from Low vitamin B
holoTC facilitate the laboratory diagnosis of cobalamin deficiency.
12
available during foetal life and later
vegetarians or vitamin low intake via human milk from deficient mothers
However, as before, there is no single ‘gold standard’ marker that
B
12
-deficient mothers
can be applied for all clinical conditions.
Elderly Pernicious anaemia, achlorhydia, gastrointestinal
diseases or drugs that alter pH, ileum resection,
Risk Groups Helicobacter pylori
The prevalence of subclinical functional vitamin B
12
deficiency is Neurodegenerative and Either causally related to the clinical symptoms or
higher than expected when sensitive and relatively specific
psychiatric diseases secondary to the disease because of low intake
markers are used such as MMA, holoTC and Hcy.
15,16
Risk groups for
Chronic atrophic gastritis Malabsorption of vitamin B
12
vitamin B
Diseases of the Crohn’s disease, ileum resection,
12
deficiency (see Table 1) include: patients with
unexplained anaemia; patients with unexplained neuropsychiatric
terminal ileum bacterial overgrowth
Macrocytic anaemia Low B
symptoms; patients with gastrointestinal manifestations, including
12
intake or pernicious anemia
(antibodies against intrinsic factor)
stomatitis, anorexia and diarrhoea; elderly people;
15
vegetarians;
4
Chronic alcoholism Low intake, disturbed absorption of the vitamin
patients with gastrointestinal disorders, such as Crohn’s disease or
Medications Proton pump inhibitors, H2-receptor antagonists,
infection with Helicobacter pylori; and patients with stomach
nitric oxide exposure
resection.
17
To date, the rate of people in the at-risk population who
AIDS-associated Abnormal vitamin B
12
utilsation
will develop clinical symptoms because of vitamin B
12
deficiency myelopathy
has not been studied systematically.
vitamin B
22
12
deficiency. In 40% of patients, serum concentrations of
In the general population, the prevalence of vitamin B
12
deficiency in B
12
rose after treatment for H. pylori infection. According to recent
younger people is 5–7%.
18
Functional vitamin B
12
deficiency – i.e. reports, longer-term treatment of H. pylori (one year) resulted in a
raised MMA and lowered holoTC – is common in old age and has significant rise in mean vitamin B
12
(from 146 to 271pmol/l) and a fall
been diagnosed in 10–30% of patients over 65 years of age.
16
A high in mean Hcy concentrations (from 41 to 13µmol/l).
23
Vitamin B
12
prevalence of a slightly abnormal vitamin B
12
status has been malabsorption owing to H. pylori infection can thus lead to vitamin
reported in elderly people despite intake of the recommended daily B
12
deficiency and hyperhomocysteinaemia.
dose (>2.4µg/day). This deficiency is not presumed to be associated
with dietary causes but rather with malabsorption.
19
Fifty-three per Vegetarians are at high risk of developing vitamin B
12
deficiency
cent of elderly patients from Strasbourg who had vitamin B
12
because animal products are the main sources of vitamin B
12
.A
deficiency had malabsorption problems and 33% had pernicious functional B
12
deficiency (lowered holoTC, raised MMA and Hcy) is
anaemia; in only 2% was vitamin B
12
deficiency related to insufficient common in vegetarians and depends on the strictness of the diet
and the amount of time for which the vegetarian diet has been
followed.
4
Persons with an increased vitamin requirement – such as
To date, the rate of people in the
pregnant and breastfeeding women, patients with autoimmune
disorders or persons with HIV infection – are a further risk group for
at-risk population who will develop
vitamin B
12
deficiency. Persons who regularly take proton pump
clinical symptoms because of
inhibitors can also develop vitamin B
12
deficiency.
vitamin B
12
deficiency has not been
Vitamin B
12
deficiency is also widespread in patients with renal
studied systematically.
disorders.
13
In spite of normal plasma concentrations of vitamin B
12
or holoTC, these patients often have raised serum concentrations of
MMA and Hcy.
13
The likely cause is disrupted cellular absorption
dietary intake, and in 11% the aetiology of the vitamin B
12
deficiency of holoTC, which results in intracellular vitamin B
12
deficiency and
remained unexplained.
20
However, because the currently raised metabolites. Studies have shown that patients with renal
recommended dietary intake for vitamin B
12
in elderly people is low, disorders may have higher concentrations of holoTC, which seems
dietary deficiencies are underdiagnosed. Using synthetic vitamin B
12
to contradict vitamin B
12
deficiency.
13,24
This can be explained by the
preparations can protect elderly persons from symptoms of role of the kidney in transcobalamin filtration and resultant
deficiency.
21
However, dietary intake of vitamin B
12
does not provide secondary accumulation of holoTC. The plasma concentration of
any information on vitamin B
12
status because malabsorption is a holoTC in such patients therefore does not correctly reflect the
common and important factor. Furthermore, elderly persons often functional vitamin B
12
status.
13
have atrophic gastritis, pernicious anaemia or achlorhydria.
Disorders that affect the gastrointestinal pH can also result in Utility of Holotranscobalamin as an
malabsorption and thus vitamin B
12
deficiency. The incidence of Early Diagnostic Marker
H. pylori is high in elderly people and can lead to atrophic gastritis, Recent studies have emphasised the need for testing the clinical
and in turn to B
12
malabsorption, owing to disrupted production of utility of holoTC compared with vitamin B
12
and MMA. The pros and
hydrochloric acid.
2
H. pylori was found in 56% of patients with cons of the different laboratory tests of cobalamin status have
EUROPEAN HAEMATOLOGY 9
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