Folate-induced remission in aplastic anemia with familial defect of cellular folate uptake

N Engl J Med. 1978 Mar 2;298(9):469-75. doi: 10.1056/NEJM197803022980901.


Severe aplastic anemia developed in a young man with an extensive family history of leukemia, pancytopenia, and neutropenia. Megaloblastic changes became evident, and treatment with high doses of folic acid resulted in striking clinical improvement. However, red-cell folate levels remained persistently low despite high serum folate levels. A defect in cellular folate uptake was suspected, and, indeed, uptake of 5-14CH3-H4-folate by stimulated lymphocytes and by bone-marrow cells from the patient was significantly reduced (P less than 0.05 as compared to normal cells. Further characterization of folate metabolism showed that intestinal absorption of the vitamin, membrane transport of 5-14CH3-H4-folate by mature red cells, folate utilization in the conversion of deoxyuridylate to thymidylate and polyglutamate formation were all normal. At least five other family members manifest decreased uptake of 5-14CH3-H4-folate by stimulated lymphocytes. These studies suggest that a genetically induced abnormality of folate uptake contributed to this patient's severe, but reversible, aplasia.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anemia, Aplastic / drug therapy
  • Anemia, Aplastic / metabolism*
  • Blood Cells / metabolism*
  • Bone Marrow / metabolism
  • Bone Marrow Cells
  • Cells, Cultured
  • Erythrocytes / metabolism
  • Folic Acid / administration & dosage
  • Folic Acid / metabolism*
  • Folic Acid / therapeutic use
  • Folic Acid Deficiency / genetics
  • Folic Acid Deficiency / metabolism*
  • Hematologic Diseases / genetics
  • Hematologic Diseases / metabolism
  • Hematopoiesis
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Pedigree


  • Folic Acid