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BASICS

  • Vitamin B12 (cobalamin) is essential for CNS myelination, red blood cell production, immune cell development, and DNA synthesis.
  • Deficiency causes hematologic abnormalities (megaloblastic anemia), neuropsychiatric changes (demyelination of spinal cord, peripheral nerves), and glossitis.
  • MMA and homocysteine levels are sensitive and specific markers; MMA elevated in deficiency.

EPIDEMIOLOGY

  • Prevalence is 6.9% to 15% overall; up to 30-40% in elderly institutionalized patients.
  • Higher prevalence in >60 years age group.
  • Increasingly recognized in exclusively breastfed infants of deficient mothers.
  • Macrocytosis causes include B12 deficiency (~20% of cases).

ETIOLOGY AND PATHOPHYSIOLOGY

  • Decreased intake: vegans, vegetarians.
  • Decreased intrinsic factor (IF): pernicious anemia (autoantibodies against parietal cells or IF), chronic atrophic gastritis, gastrectomy.
  • Malabsorption: Crohn disease, celiac disease, ileal resection, pancreatic insufficiency, H. pylori infection.
  • Medications: PPIs, H2 blockers, metformin interfere with absorption.
  • Rare hereditary causes: Imerslund-Gräsbeck disease (defective ileal uptake).

COMMONLY ASSOCIATED CONDITIONS

  • Gastric pathologies: pernicious anemia, gastritis, gastrectomy.
  • Small bowel disease: malabsorption syndromes, IBD.
  • Dietary insufficiency: breastfed infants of deficient mothers.
  • Medication effects: metformin, PPIs, nitrous oxide abuse.

DIAGNOSIS

History

  • Fatigue, depression, glossitis, paresthesias, ataxia, cognitive impairment.
  • Falls due to proprioception loss.
  • GI symptoms: nausea, diarrhea, abdominal pain.

Physical Exam

  • Glossitis, pallor, neurologic deficits (impaired vibration, proprioception, positive Babinski).
  • Lymphadenopathy, hepatosplenomegaly.

Laboratory Tests

  • Serum vitamin B12: low (<200 pg/mL diagnostic; 150-399 pg/mL borderline).
  • Elevated MMA and homocysteine: more sensitive/specific.
  • CBC: macrocytic anemia (may be masked).
  • Antibodies: anti-IF (50-70% sensitivity), anti-parietal cell (less specific).
  • Elevated serum gastrin if pernicious anemia suspected.

TREATMENT

  • Parenteral cyanocobalamin for severe deficiency or neurologic symptoms:
  • IM 1000 µg every other day for 1-2 weeks, then weekly for 1 month, then monthly lifelong if pernicious anemia.
  • High-dose oral cyanocobalamin (1000-2000 µg daily) may be effective in some cases.
  • Avoid folic acid monotherapy in pernicious anemia to prevent worsening neurologic damage.
  • Address underlying causes (e.g., diet, medications).

PEDIATRIC AND PREGNANCY CONSIDERATIONS

  • Deficiency in pregnancy increases risk of neural tube defects, developmental delays.
  • Breastfed infants of deficient mothers at risk for neurologic and hematologic complications.
  • Early diagnosis and treatment critical.

ONGOING CARE

  • Monitor hematologic response (reticulocytosis within 1 week, hemoglobin normalization 6-8 weeks).
  • Neurologic improvement can take months; some symptoms may be irreversible.
  • Monitor potassium levels in severe anemia.

PROGNOSIS

  • Generally good with treatment, but neurologic recovery may be incomplete in longstanding cases.
  • Persistent symptoms warrant reassessment.

COMPLICATIONS

  • Neurologic: peripheral neuropathy, subacute combined degeneration of spinal cord, cognitive impairment.
  • Hematologic: macrocytic anemia, pancytopenia.
  • Neuropsychiatric: depression, psychosis, memory loss.

REFERENCES

  1. Layden AJ, Täse K, Finkelstein JL. Neglected tropical diseases and vitamin B12: a review of the current evidence. Trans R Soc Trop Med Hyg. 2018;112(10):423-435.
  2. Vincenti A, Bertuzzo L, Limitone A, et al. Perspective: practical approach to preventing subclinical B12 deficiency. Nutrients. 2019;11(3):596.
  3. Devi A, Rush E, Harper M, et al. Vitamin B12 status of various ethnic groups living in New Zealand: an analysis of the Adult Nutrition Survey 2008/2009. Nutrients. 2018;10(2):181.

ICD10

  • D51 Vitamin B12 deficiency anemia
  • D51.8 Other vitamin B12 deficiency anemia

Clinical Pearls

  • Common presenting symptoms: fatigue, glossitis, neuropathy (stocking-glove), depression, falls.
  • Pernicious anemia requires lifelong cyanocobalamin replacement.
  • MMA and homocysteine help clarify diagnosis in borderline B12 levels.
  • Avoid folic acid monotherapy in pernicious anemia to prevent neurologic damage.