V. Herbert; Trans Assoc Am Phys 1962;75:307

Cause:

• Dietary: poor, pregnant (18% Boston City Hospital pregnant females—Nejm 1967;276:776), and/or alcoholic
• Inadequate absorption: small bowel disease, throughout length, eg, sprue, blind loop
• Antifolate drugs most of which inhibit deconjugase in gut mucosa since only monoglutamic folate readily absorbed (Nejm 1969;280:985): alcohol, Dilantin, mysoline, birth control pills (Nejm 1970;282:858), triamterine (Ann IM 1970;73:414), pyramethamine, chemotherapy, esp with methotrexate

Pathophys:Minimum daily requirement is 50 µgm/d in adults and children; 400 µgm/d in pregnancy. Reserves last 3-6 mo. Polyglutamic folic acid is present in meat, eggs, cow's (not goat's) milk products, vegetables (prolonged steaming will leach out); necessary for thymidylate synthesis (the important one), histidine catabolism (FIGLU an intermediate), methionine synthesis, and 2 steps in purine metabolism

Sx:of anemia—sore tongue and mouth, diarrhea

Si:Glossitis, stomatitis, hemolytic jaundice

Anemia in 20 weeks after intake becomes zero; megaloblasts and some anemia after 40-60 d (R. Hillman—Nejm 1971;284:933)

Bleeding in pregnancy (Nejm 1967;276:776); increased MI and other ASCVD risk even w/o anemia, probably via incr homocysteine (Jama 1996;275:1893)

r/o other megaloblastic anemias (Nejm 1973;288:764): B₁₂ deficiency, orotic aciduria (Nejm 1990;322:1641, 1652), Di Guglielmo's syndrome, anti-DNA drugs

Lab:

Chem:Serum folate level by radioimmunoassay (Nejm 1972;286:764); increased homocysteine levels, but not MMA levels

Hem:Anemia, macrocytic with macro-ovalocytes; neutropenia and hypersegmented polys; platelets normal or low unlike Fe deficiency

Path:Marrow is megaloblastic with giant “C” metamyelocytes (bands); macrocytic cells elsewhere too, eg, gut mucosa (Nejm 1970;282:859)

Rx:Being added to cereal products to decr congenital spinal abnormalities and for possible beneficial effects on heterozygous homocysteinemia

Monoglutamic folic acid 1 mg po qd is twice the adequate replacement dose; BEWARE, doses of 15 mg qd will reverse B₁₂ anemia but not the neurologic deficits (Arch IM 1960;105:372)