• Clinical science

Folate deficiency (Folic acid deficiency…)

Abstract

Folate (vitamin B9) is an essential coenzyme that enables critical biochemical reactions. Dietary sources include naturally folate-rich foods such as leafy green vegetables, fruit and liver, but also supplements and fortified foods. Malnutrition and excessive alcohol use are the most common causes of deficiency. Folate deficiency causes impaired DNA synthesis, which leads to megaloblastic anemia. The clinical picture of anemia is similar to that of vitamin B12 deficiency, although folate deficiency is generally not associated with neurological manifestations. Diagnosis is based on laboratory findings such as macrocytosis, hyperhomocysteinemia, and normal levels of methylmalonic acid. Therapy consists of oral supplementation.

Physiology

Etiology

References:[1][2]

Pathophysiology

  • FolateTHF
    • DNA synthesis → megaloblastic erythropoiesis megaloblastic anemia (+ ↓ in other cell lines)
    • → ↓ methionine + homocysteineendothelial damage (→ ↑ risk of cardiovascular disease)
    • During fetal development: → nucleotide synthesis impairment → neural tube defects
    • → Aberrant DNA methylation → increased risk of cancer

Clinical features

  • Signs of anemia (e.g., fatigue, pallor)
  • Sore tongue (glossitis )

Unlike in vitamin B12 deficiency, folate deficiency does not result in neurological symptoms!

Diagnostics

  • MCV (> 100 μm3)
  • homocysteine
  • Methylmalonic acid (MMA) is normal (unlike in vitamin B12 deficiency, where MMA is ↑)
  • Hypersegmented neutrophils and pancytopenia may be present
  • Folate serum levels are not reliable

If folate deficiency is suspected, always exclude the possibility of vitamin B12 deficiency!

References:[3]

Treatment

  • Oral folate supplementation for four months or until hematologic recovery takes place
  • Nutritional counseling to increase folate intake

Because of the risk of neural tube defects, it is recommended that women planning to become pregnant initiate folate supplementation before conception!

References:[4]