Vitamin B12 (cobalamin) deficiency classically presents with megaloblastic anemia, but can also present with neurologic and neuropsychiatric complaints.
Older people, patients with chronic malabsorption, patients with a history of gastric resection or bypass, and those taking certain medications (metformin, proton-pump inhibitors) are at risk.
Early diagnosis is critical in preventing and halting the progression of neurologic disorders such as peripheral neuropathy, subacute combined degeneration of the spinal cord, and dementia.
Methylmalonic acid and homocysteine levels may help to diagnose vitamin B12 deficiency at an early, asymptomatic state.
Cause of vitamin B12 deficiency should be searched for once a diagnosis is confirmed.
Treatment with high-dose oral vitamin B12 therapy may be as effective as intramuscular vitamin B12 therapy.
Vitamin B12 is an essential vitamin; deficiency generally occurs with inadequate absorption or lack of dietary intake.
Vitamin B12 deficiency is a common condition that can manifest with neurologic, psychiatric, and hematologic disorders. While severe deficiency can cause permanent neurologic damage, earlier manifestations are generally subtle or asymptomatic.
The likelihood of vitamin B12 deficiency can be defined according to the serum vitamin B12 level as follows: <200 picograms/mL indicates probable deficiency; 201 to 350 picograms/mL indicates possible deficiency; and >350 picograms/mL indicates that deficiency is unlikely.
Vitamin B12 level >350 picograms/mL does not exclude vitamin B12 deficiency, particularly if pernicious anemia is suspected. Spuriously normal or high serum vitamin B12 levels have been reported in patients with pernicious anemia due to anti-intrinsic factor antibody (anti-IFAB) interference in laboratory assays.
History and exam
Key diagnostic factors
- old age
- history of gastric surgery (gastrectomy, or bypass for obesity)
Other diagnostic factors
- vegan and strict vegetarian diet
- chronic gastrointestinal disease (e.g., Crohn disease or celiac disease)
- medication (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants)
- decreased vibration sense
- positive Romberg test
- angular cheilitis
- cognitive impairment
- age >65 years
- gastric surgery (bypass or resection)
- chronic gastrointestinal (GI) disease
- vegan or strict vegetarian diet
- metformin use
- H2 receptor antagonist or proton-pump inhibitor use
- Helicobacter pylori infection
- anticonvulsant use
- nitrous oxide misuse
- diabetes mellitus
1st investigations to order
- peripheral blood smear
- serum vitamin B12
- reticulocyte count
Investigations to consider
- methylmalonic acid (MMA)
- holotranscobalamin (hTC)
- anti-intrinsic factor antibody (anti-IFAB)
- antiparietal cell (APC) antibody
- serum gastrin (fasting)
asymptomatic or borderline deficiency
- Folic acid (vitamin B9) deficiency
- Myelodysplastic syndrome (MDS)
- Alcoholic liver disease
- Cobalamin (vitamin B12) and folate deficiency
- ESPEN micronutrient guideline
Vitamin B12 deficiency
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