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Holotranscobalamin – An Early Marker for Laboratory Diagnosis of Vitamin B
12
Deficiency
concentrations of MMA above 300nmol/l in individuals with normal should be started. A significant reduction of serum MMA (by
renal function showed a larger area under the curve (AUC) for approximately 250nmol/l) after cobalamin treatment indicates a
holoTC compared with vitamin B
12
(0.71 versus 0.60). This supports pre-treatment deficiency. A residual increment of MMA is then
a better diagnostic sensitivity and specificity for holoTC compared related to renal dysfunction. We have suggested an algorithm for
with vitamin B
12
. A 72% sensitivity could be expected by using a laboratory diagnosis of vitamin B
12
deficiency (see Figure 6). This
cut-off of 35pmol/l for holoTC and 243pmol/l for vitamin B
12
. algorithm takes into account renal dysfunction as a common cause
for elevated both holoTC and MMA.
Renal insufficiency constitutes a common and important
exceptional condition for the interpretation of cobalamin markers. Screening
The artificial increase of serum concentrations of MMA and tHcy in At present there is no consensus regarding screening for vitamin B
12
some clinical settings is a major limitation of these parameters.
30
deficiency. Screening makes sense when the first signs of vitamin B
12
Both parameters correlate to serum concentration of creatinine deficiency can be detected before neurological or haematological
and increase even in mild degrees of renal insufficiency.
31
In anomalies develop. HoloTC and MMA are suitable screening tools;
general, results of the metabolites should be interpreted with however, renal dysfunction should be kept in mind. ■
caution because it is difficult to determine the extent to which the
impaired kidney function may participate in MMA and Hcy
Wolfgang Herrmann is a Senior Scientist in the
elevation.
31
Cobalamin deficiency is common in patients with renal
Department of Clinical Chemistry and Laboratory
dysfunction. Moreover, concentrations of holoTC in people with
Medicine at Saarland Hospital in Homburg. He is a
renal insufficiency are markedly elevated and they are not
founding member and Chairman of the Homocysteine
Expert Panel. Professor Herman has published
consistent with what we have learned about vitamin B
12
deficiency.
approximately 250 articles, half of which involve
This one important exception is relatively common and may raise
research results related to the topic of homocysteine,
some uncertainty about using holoTC as a marker of cobalamin
and he is co-author of the textbook Laboratory and
Diagnosis. He is on the Advisory Board of the German
status in renal patients and in elderly people even with subclinical
Society for Atherosclerosis Research.
degrees of renal insufficiency. A laboratory diagnosis of cobalamin
deficiency in renal patients is an important challenge that remains
Rima Obeid is a Junior Professor in the Department of
Clinical Chemistry and Laboratory Medicine at the
unresolved because of the simultaneous increase of both serum
University of Saarland in Homburg. She completed her
MMA and holoTC. Our observations of patients with renal
post-doctoral fellowship (Alexander von-Humboldt
dysfunction or elderly people with mild renal complications
Foundation) in 2005 at the same institution. Prior to
this, she completed a diploma in clinical biochemistry in
suggest that cobalamin deficiency in these patients can be ruled
the Department of Clinical Biochemistry, College of
out only after cobalamin treatment. Whenever cobalamin
Pharmacy at Damascus University.
deficiency is suspected in renal patients, cobalamin treatment
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EUROPEAN HAEMATOLOGY 11
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