Updated: 4/16/2018

Folic Acid Deficiency

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  • A 25-year-old woman presents to her obstetrician at 22-weeks pregnant. She had no previous prenatal care but denies any problems. She denies taking any vitamin supplements.  She is doing well in her first pregnancy and finally came for prenatal care at the urging of her mother. She is notably pale. Bloodwork reveals megaloblastic anemia and she is started on folic acid supplementation immediately. However, she is counseled on the possible affects folic acid deficiency may have on the baby.

  • Folic acid (or vitamin B9) is found in leafy green vegetables
  • Pathogenesis
    • folic acid is absorbed in jejunum and ileum
      • used in tetrahydrofolate (THF) as coenzyme
      • important for DNA and RNA synthesis
      • small reserve pool in liver
      • see Vitamins topic 
    • causes megaloblastic anemia due to impaired DNA synthesis
  • Epidemiology
    • most common vitamin deficiency in the US
    • most common cause of megaloblastic anemia
    • can manifest after 4 months (depleted storage from liver)
  • Associated conditions
    • chronic hemolytic anemias
    • alcoholism
    • malabsorption
      • celiac disease
      • tropical sprue
    • pregnancy
      • risk of neural tube defects in infant
    • certain drugs (anti-folates)
      • phenytoin
      • methotrexate
  • Symptoms
    • no neurological symptoms (unlike in B12 deficiency)
    • anemia
      • fatigue
      • weakness
      • shortness of breath
  • Physical exam
    • glossitis
    • pallor
  • Peripheral blood smear
    • hypersegmented lobes seen in neutrophils
    • macrocytosis
  • Serum 
    • ↓ folic acid
    • ↑ homocysteine
    • NORMAL methylmalonic acid (MMA)
      • unlike in vitamin B12 deficiency, which has ↑MMA
Differential Diagnosis
  • Vitamin B12 deficiency
  • Pernicious anemia
  • Other causes of macrocytic anemia
    • alcoholism
    • hypothyroidism
    • liver dysfunction
    • drugs
  • Folic acid supplementation
  • Eat a more balanced diet
    • fruits and vegetables
Prognosis, Prevention, and Complications
  • Prognosis
    • good with supplementation
  • Prevention
    • folic acid supplementation, especially if chronically on drugs such as methotrexate
  • Complications
    • neural tube defects in infant if deficient during pregnancy
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