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Anaemia and Haemoglobinuria
Holotranscobalamin – An Early Marker for
Laboratory Diagnosis of Vitamin B
12
Deficiency
Wolfgang Herrmann
1
and Rima Obeid
2
1. Senior Scientist; 2. Junior Professor, Department of Clinical Chemistry and Laboratory Medicine, University Hospital Homburg, Saarland University
Abstract
Vitamin B
12
deficiency is widespread. Among the population groups at risk are older people, vegetarians, pregnant women and patients
with renal or intestinal diseases. The neurological symptoms of vitamin B
12
deficiency are unspecific and can be irreversible. Early detection
is therefore important. This article reviews the diagnostic performance of the different laboratory markers for vitamin B
12
status. Total
serum vitamin B
12
is a relatively insensitive and unspecific biomarker of deficiency that does not reflect recent variations in cobalamin
status. Holotranscobalamin (holoTC), the metabolically active portion of vitamin B
12
, is the earliest laboratory parameter that becomes
decreased in case of a vitamin B
12
negative balance. Concentration of methylmalonic acid (MMA) is a functional vitamin B
12
marker that
will increase when the vitamin B
12
stores are depleted. Isolated lowering of holoTC shows vitamin B
12
depletion (negative balance), while
lowered holoTC plus elevated MMA (and homocysteine) indicates a metabolically manifested vitamin B
12
deficiency, although there still
may be no clinical symptoms. The diagnostic use of holoTC allows the initiation of therapeutic measures before irreversible neurological
damage develops. Because the clinical manifestations of vitamin B
12
deficiency are unspecific, people at risk should be identified and
should regularly test their holoTC with or without MMA.
Keywords
Cobalamin, holotranscobalamin, diagnosis, deficiency
Disclosure: The authors have no conflicts of interest to declare.
Received: 9 July 2009 Accepted: 4 August 2009
Correspondence: Wolfgang Herrmann, Klinische Chemie und Laboratoriumsmedzin, Universitätsklinikum des Saarlandes, Gebäude 57, D-66421 Homburg, Germany.
E:
kchwher@uniklinikum-saarland.de
Pernicious anaemia, which causes severe vitamin B
12
(cobalamin) estimated stores of vitamin B
12
in the human liver are relatively
deficiency, used to be a fatal, non-curable disease. However, in high.
1
Therefore, in the case of intact absorption, the depletion of
1926 George Minot and William Murphy discovered that pernicious the vitamin takes years to be expressed as a metabolic or clinical
anaemia can be treated by including large amounts of liver in dysfunction. Acquired vitamin B
12
deficiency can be related to
patients’ food. Vitamin B
12
is synthesised exclusively in micro- prolonged insufficient intake, disturbed absorption, increased
organisms. Animals obtain vitamin B
12
from foods contaminated requirements or an accelerated loss of the vitamin.
with vitamin B
12
-synthesising bacteria, and thus foods of animal
origin represent the only source of vitamin B
12
in the human diet. Subtle Vitamin B
12
Deficiency and
Recommended Daily Amount
Together with 5-methyltetrahydrofolate, vitamin B
12
is an essential Subtle vitamin B
12
deficiency is common in the general population
co-factor in methyl group transfer, cell division and catabolism of and it is more widespread than has been assumed so far.
2–4
Chronic
homocysteine (Hcy). In addition, vitamin B
12
is required by all cells insufficient intake or disrupted absorption of vitamin B
12
are the most
for one-carbon metabolism and DNA synthesis and maintenance. common causes of cobalamin deficiency.
Only two vitamin B
12
-dependent enzymes are known in humans:
methionine synthase and L-methylmalonyl-CoA mutase. Methionine According to the recommended daily amount (RDA) guidelines from
synthase mediates the formation of methionine from Hcy, and the National Research Council of the US National Academy of
requires methylcobalamin as a co-factor. L-methylmalonyl-CoA Sciences, adults should ingest 2.4µg daily (pregnant women up to
mutase requires adenosylcobalamin, and catalyses the formation of 6µg), which can be met by a typical western diet.
5
The calculation of
succinyl-CoA from methylmalonyl-CoA. The latter compound can be the required amount is based on the calculation of the amount
converted into methylmalonic acid (MMA). Serum concentrations of vitamin B
12
necessary to sustain a normal haematological status
of MMA and Hcy are therefore considered metabolic indicators of (normal haemoglobin and mean corpuscular volume of erythrocytes
vitamin B
12
status. [MCV]) and to maintain remission in pernicious anaemia. At the time
when the RDA was set, functional metabolic markers of vitamin B
12
Vitamin B
12
is conserved in humans through the enterohepatic had not been sufficiently investigated in clinical studies.
circulation and via active re-absorption in the proximal tubule. The Neurological manifestations are found at a relatively late stage of
© TOUCH BRIEFINGS 2009 7
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