Hematology · USMLE Step 1 and Step 2

Megaloblastic Anemia - Folate song

Megaloblastic Anemia: Folate Deficiency, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Megaloblastic Anemia - Folate

Full song on YouTube ↗Spotify ↗

Key points in this song10

Folate deficiency causes megaloblastic anemia by impairing thymidylate synthesis, leading to defective DNA synthesis and megaloblastic changes in rapidly dividing cells.
Unlike B12 deficiency, folate deficiency does NOT cause subacute combined degeneration of the spinal cord (no neurological symptoms).
Classic at-risk populations include alcoholics, pregnant women, patients on methotrexate or trimethoprim, and those with malabsorption (e.g., celiac disease).
Methotrexate and trimethoprim cause functional folate deficiency by inhibiting dihydrofolate reductase (DHFR), blocking conversion of folate to its active tetrahydrofolate (THF) form.
Lab findings include elevated MCV (macrocytosis), hypersegmented neutrophils (≥5 lobes), elevated homocysteine, and normal methylmalonic acid (MMA) — distinguishing it from B12 deficiency.
Serum folate reflects recent dietary intake; RBC folate is a more reliable marker of long-term folate stores.
Folate is absorbed in the jejunum and requires adequate dietary intake (green leafy vegetables, legumes); body stores last only 3–4 months, making deficiency develop faster than B12 deficiency.
Periconceptional folate supplementation (400–800 mcg/day) reduces the risk of neural tube defects (spina bifida, anencephaly).
Leucovorin (folinic acid) is used to rescue cells from methotrexate toxicity by bypassing the DHFR blockade.
Both folate and B12 deficiency cause elevated homocysteine, but only B12 deficiency elevates methylmalonic acid — this distinction is a classic USMLE discriminator.