TRAINING and EDUCATION
You Make the Call
Each month in “You Make the Call,” we pick a challenging clinical question submitted through the Consult a Colleague program
and post the expert’s response, but we also want to know what you would do. Send in your response to next month’s clinical
dilemma and see how your answer matches up to the expert’s in the next print issue.
This month, Marilyn Telen, MD, discusses management of a patient with long-term B 12 deficiency.
Clinical Dilemma:
I have a 42-year-old female patient who has had very low B 12 levels for at least a decade. This is the first time she has
seen a hematologist. She does not have persistent anemia or red cell macrocytosis. She has no neurologic symptoms.
Her methylmalonic acid levels and B 12 -binding capacity have been normal. She has had a lot of gastrointestinal issues
and, at various times, small bowel Crohn disease as well as small intestine bacterial overgrowth, which have required
therapy. At this time, she is not on any treatment other than dietary restrictions and desipramine. Serology for
pernicious anemia and bowel biopsies looking for celiac disease have been normal.
In the past her B 12 level has increased moderately when given supplementation, but she does not tolerate parenteral,
oral, or nasal supplementation so stopped them. As far as she knows, there is no family history of B 12 issues. My best
guess is that she has some form of B 12 -binding protein abnormality that is not of any functional consequence. I tried to
find a way to assay for transcobalamin 1 but have not had success. Any suggestions regarding further testing, if needed,
or management are welcomed.
Expert Opinion
Consult a Colleague
Through ASH
Consult a Colleague is a service for ASH
members that helps facilitate the exchange
of information between hematologists
and their peers. ASH members can
seek consultation on clinical cases from
qualified experts in 11 categories:
• Anemias
Marilyn Telen, MD
Wellcome Professor of Medicine
Division of Hematology
Director, Duke Comprehensive Sickle Cell Center
Duke University Medical Center
• Hematopoietic cell
transplantation
• Hemoglobinopathies
• Hemostasis/thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
A longstanding “low” B 12 level in the absence of signs
and symptoms of B 12 deficiency presents an interest-
ing dilemma. Methylmalonic acid (MMA) level and
B 12 binding capacity (unsaturated transcobalamin)
levels that are not elevated support the conclusion
that the patient is not functionally B 12 deficient.
That she does not have anemia or even macrocyto-
sis also suggests that your patient is not functionally
B 12 deficient, as confirmed by her normal MMA. In
general, MMA is a much more reliable test for func-
tional B 12 deficiency than a B 12 level. You could also
get a homocysteine level if you want to reassure your
patient further. The negative personal or family history
of pernicious anemia or related autoimmune disorders
also fits with the conclusion that your patient is not truly
B 12 deficient.
There are a variety of B 12 assays that use different
methodologies, but none have proven entirely reliable
clinically, although they tend to correlate with each
other. Thus, a normal serum B 12 concentration does not
reliably rule out a functional B 12 deficiency, the assess-
ment of which is better served by homocysteine or MMA
measurement. Conversely, your patient’s results imply
that low levels also do not entirely reliably indicate true
functional B 12 deficiency.
I doubt that your patient has an inherited abnormality
of transcobalamin, given that she seems relatively healthy
and has a normal unsaturated transcobalamin level. Most
transcobalamin deficiency is caused by mutations in the
TCN2 (transcobalamin 2) gene and lead to a complete
or near-complete deficiency of transcobalamin. Most pa-
tients with inherited transcobalamin disorders are detect-
ed due to anemia and even failure to thrive when they are
quite young. All such patients appear to have low results
in assays of B 12 -binding capacity. There are some links
to available testing for transcobalamin 2 (see the NIH
Genetics and Rare Diseases Information Center), but I do
not think such testing is indicated for your patient.
ASHClinicalNews.org
• Multiple myeloma & Waldenström
macroglobulinemia
• Myeloproliferative neoplasms
• Myelodysplastic syndromes
• Thrombocytopenias
Assigned volunteers (“colleagues”) will
respond to inquiries within two business
days (either by email or phone).
Have a puzzling clinical dilemma?
Submit a question, and read more
about Consult a Colleague volunteers at
hematology.org/Clinicians/Consult.aspx
or scan the QR code.
All that being said, inability to tolerate B 12 supplements
of any sort is rare. B 12 is, in my experience, among the
best-tolerated medicines I have ever prescribed. However,
some people may experience adverse reactions, including
headache, gastrointestinal distress (nausea, diarrhea),
pruritus, and nervousness or anxiety. It would be reason-
able to encourage her to eat B 12 -rich foods, such as fish,
meat, poultry, eggs, milk, and milk products. Continued
surveillance for functional B 12 deficiency (such as annual
MMA measurement) might also be reasonable, given the
sometimes serious consequences of true B 12 deficiency.
Next Month’s Clinical Dilemma:
I have a patient with a strong family history of chronic
lymphocytic leukemia (CLL) who was recently diag-
nosed with CLL. Her mother and brother have CLL as
well. What is the status of familial CLL? Has a gene
been identified as of yet?
How would you respond? Email us at
[email protected]. ●
* If you have a request related to a
hematologic disorder not listed here,
please email your recommendation to
[email protected] so it can be
considered for addition in the future.
DISCLAIMER: ASH does not recommend
or endorse any specific tests, physicians,
products, procedures, or opinions, and
disclaims any representation, warranty, or
guaranty as to the same. Reliance on any
information provided in this article is solely
at your own risk.
ASH Clinical News
29