Vitamins B9 and B12 Deficiencies

Summary

Megaloblastic anemia is a macrocytic anemia caused by deficiencies of either Folate (Vitamin B9) or Cobalamin (Vitamin B12). Megaloblastic anemia is characterized by the presence of hypersegmented neutrophils (>5 lobes) in peripheral blood smears, and labs reveal elevated homocysteine levels. Despite these similarities, there are distinguishing characteristics between folate and cobalamin deficiency.

Cobalamin (B12) deficiency is characterized by neurologic symptoms, as myelin synthesis is impaired in a syndrome known as subacute combined degeneration. Specifically, the lateral corticospinal tract, spinocerebellar tract, and dorsal columns are affected. Labs show elevated methylmalonic acid (MMA) levels, a finding not observed in folate deficiency.

Contrastingly, Folate (B9) deficiency is more common and occurs faster than B12 deficiency, as the liver has a smaller reserve pool of folate. Folate deficiency is common in alcoholics, and is often seen in conjunction with Vitamin B1 (Thiamine) Deficiency.

Key Points

• Folate (B9) and Cobalamin (B12) Deficiency
  • Common in both deficiencies
    • Hypersegmented neutrophils (polymorphonuclear cells, PMNs)
      • presence of >5 lobes
    • Elevated homocysteine
      • Defective conversion to methionine (see Homocysteine Metabolism)
    • Glossitis (less important)
  • Unique in Cobalamin (B12) Deficiency
    • large reserve pool in liver (lasts several years)
    • seen with:
      • lack of intrinsic factor
        • pernicious anemia (atrophic gastritis), gastric bypass
      • impaired absorption at terminal ileum
        • surgical removal of ileum in Crohn’s disease
      • malabsorption
        • sprue, enteritis, Diphyllobothrium latum
      • poor intake
        • strict vegetarian diets
    • elevated methylmalonic acid (MMA) levels
      • contrast vs. folate deficiency
    • irreversible neurological damage
      • subacute combined degeneration
        • degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts
      • paresthesias also seen
  • Unique in Folate (B9) Deficiency
    • small reserve pool in liver (lasts 3-4 months)
    • most common vitamin deficiency in US, seen in:
      • alcoholics and the malnourished
      • with taking certain drugs (methotrexate, phenytoin, sulfonamides)
    • normal methylmalonic acid (MMA) levels
      • contrast vs. cobalamin deficiency
    • neural tube defects (in pregnancy)
      • high-dose folate supplementation recommended

Find Vitamin B9 and B12 Deficiency and other Vitamins among Pixorize's visual mnemonics for the USMLE Step 1 and NBME shelf exams.