Vitamin B12 deficiency classically presents with megaloblastic anaemia, but can also present with neurological and neuropsychiatric complaints.
Older people, patients with chronic malabsorption, patients with a history of gastric resection or bypass, and those taking certain medicines (metformin, proton-pump inhibitors) are at risk.
Early diagnosis is critical in preventing and halting the progression of neurological disorders such as peripheral neuropathy, sub-acute 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 deficiency is a common condition that can manifest with neurological, psychiatric, and haematological disorders.
Vitamin B12 is an essential vitamin, and deficiency generally occurs with inadequate absorption or lack of dietary intake. While severe deficiency can cause permanent neurological 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: <148 picomols/L (<200 picograms/mL) indicates probable deficiency; 148 to 258 picomols/L (201-350 picograms/mL) indicates possible deficiency; and >258 picomols/L (>350 picograms/mL) indicates that deficiency is unlikely.
Vitamin B12 level >258 picomols/L (>350 picograms/mL) does not exclude vitamin B12 deficiency, particularly if pernicious anaemia is suspected. Spuriously normal or high serum vitamin B12 levels have been reported in patients with pernicious anaemia due to anti-intrinsic factor antibody (anti-IFAB) interference in laboratory assays.
History and exam
Key diagnostic factors
- presence of risk 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's disease or coeliac disease)
- medicine (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants)
- decreased vibration sense
- positive Romberg's test
- angular cheilitis
- cognitive impairment
- age >65 years
- gastric surgery (bypass or resection)
- chronic gastrointestinal (GI) disease
- vegan diet
- metformin use
- H2 receptor antagonist or proton-pump inhibitor use
- Helicobacter pylori infection
- anticonvulsant use
- diabetes mellitus
1st investigations to order
- peripheral blood smear
- serum vitamin B12
- reticulocyte count
Investigations to consider
- methylmalonic acid (MMA)
- anti-intrinsic factor antibody (anti-IFAB)
- antiparietal cell (APC) antibody
- serum gastrin (fasting)
asymptomatic or borderline deficiency
Robert C. Oh, MD, MPH, CAQSM
Associate Chief of Staff, Education
VA Puget Sound Health Care System
RCO declares that he has no competing interests.
Thein Hlaing Oo, MD, FRCP Edin, FACP
Professor of Internal Medicine
The University of Texas MD Anderson Cancer Center
THO declares that he has no competing interests.
Rebecca Connor, MD
Section of Hematology and Oncology
Department of Internal Medicine
Wake Forest University Baptist Medical Center
RC declares that she has no competing interests.
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