Noon conference

1. Noon Conference
Julie Grossman-Kranseler
11/21/18

2. © 2016 Virginia Mason Medical Center 2
Objectives
Vitamin B12 Deficiency
• Overview of B12 importance and
prevalence of deficiency
• Etiologies
• Clinical presentation
• Diagnosis
• Treatment

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Basics
• Importance
• Binds to homocysteine or MMA to form
important metabolites for cellular and DNA
repair
• Involved in hematopoiesis and nervous
system functions
• Present in meat and animal products
• Metabolized in the stomach and absorbed
in the ileum, stored in the liver
• Prevalence:
• 3-5% in general population
• 5-20% among people >65yo
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Etiologies
• Decreased intake
• Particularly vegan diets
• Decreased absorption
• Bariatric surgery, IBD, celiac, pancreatic
insufficiency, Diphyllobothrium latum (fish
tapeworm)
• Pernicious anemia = intrinsic factor
autoantibodies
• Medications
• Metformin (due to altered Ca2+
homeostasis), PPI/H2 blockers, nitrous oxide
• Rare genetic disorders – usually AR
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Nitrous Oxide & B12
• Exposure to nitrous oxide can lead
to rapid depletion of B12
• Especially if baseline B12 levels are
borderline
• N2O inactivates B12 and impairs its
ability to act as a cofactor for
methionine synthase
• Can cause rapid neuropsychiatric
deterioration
• Less likely to have hematologic effects
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Clinical Presentation
• Macrocytic/Megaloblastic anemia
• GI: glossitis
• Skin: hyperpigmentation, hair
changes, vitiligo
• Increased risk of osteoporosis and
hip/spine fractures
• Increased risk of MI & stroke
• Increased risk of gastric cancer in
pts with pernicious anemia
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Clinical presentation
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• Neuropsychiatric:
• Symmetric paresthesias, numbness, gait
problems, abnormal DTR’s
• Subacute combined degeneration
• Affecting the dorsal and lateral columns of
the spinal cord due to demyelination
• Impaired vibration or position sense
• Visual disturbances
• Paraplegia, incontinence
• Depression, insomnia, psychosis
• 28% of pts with neuropsychiatric
abnormalities lack anemia or macrocytosis

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Question
What is the most sensitive test for the
diagnosis of vitamin B12 deficiency
A. Hgb & MCV
B. MMA & homocysteine
C. Serum B12 levels
D. IF antibodies
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Diagnosis
• CBC:
• Anemia, macrocytic RBC’s, hypersegmented neutrophils, low retic count
• MCV size be altered if there are concomitant forms of anemia
• Hgb and MCV often don’t accurately reflect B12 levels
• Serum B12 levels (only moderate correlation w/ actual tissue stores)
• <200 pg/mL = deficient
• 200-300 pg/mL = normal
• >300 pg/mL = normal (90% sensitivity)
• Could consider co-testing for serum folate levels, but not done if normal diet
• Conditions that can cause spuriously low B12 levels: occult malignancy,
myeloproliferative disorder, alcoholic liver dz, renal dz, nitrous oxide, pernicious anemia
• If borderline B12 levels, measure MMA & homocysteine
•  MMA &  homocysteine = confirms B12 deficiency
• MMA normal &  homocysteine = folate deficiency
• Normal MMA & homocysteine = excludes B12 & folate deficiencies
• Unlike B12 levels, MMA & homocysteine are >95% sensitive
• If B12 deficiency is found, should test for auto-IF antibodies (highly
sensitive, less specific)
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Treatment
• Urgent treatment for symptomatic
deficiency due to risk of irreversibility of
neurologic deficits
• Occasionally symptoms worsen before
improving after initiation of treatment
• If symptomatic: start with IV or IM and
can switch to oral therapy after symptom
resolution
• If impaired absorption: IV or IM
• If dietary deficiency: oral replacement
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References
• Oh DL. And Brown. Vitamin B12 deficiency. American
Family Physician 2003; 67: 979-986.
• Stabler, Lindebaum, and Allen. Vitamin B-12 deficiency in
the elderly: current dilemnas. American Journal of Clinical
Nutrition 1997; 66: 741-749
• Nachum-Biala Y, Troen AM. B-vitamins for neuroprotection:
narrowing the evidence gap. Biofactors. 2012 Mar-Apr.
38(2):145-150.
• Green R. Vitamin B12 deficiency from the perspective of a
practicing hematologist. Blood 2017.
• Garakani A, Jaffe RJ, Savla D, et al. Neurologic,
psychiatric, and other medical manifestations of nitrous
oxide abuse: A systematic review of the case literature.
Am J Addict 2016; 25:358.
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