Folate-Induced Remission in Aplastic Anemia with Familial Defect of Cellular Folate Uptake

Richard F. Branda, Charles F. Moldow, James R. Macarthur, Maxwell M. Wintrobe, Bruce K. Anthony, Harry S. Jacob

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27 Scopus citations

Abstract

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<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. (N Engl J Med 298:469–475, 1978) SEVERE aplastic anemia continues to be a devastating syndrome, of probable diverse causes, that often results in death within six months of diagnosis.12 Androgens and other hematinics are generally ineffective,2 3 4 and development of specific therapy has been limited by an incomplete understanding of the multiple causes of the syndrome and of diagnostic technics for its elucidation. In some patients toxins, viral infections or immunologic abnormalities have been implicated, although frequently without incontestable evidence.1 In rare past reports, defects of folic acid metabolism seem possibly to have contributed to aplasia. Thus, prolonged dietary vitamin deficiency, chemotherapy with methotrexate and folic acid.

Original languageEnglish (US)
Pages (from-to)469-475
Number of pages7
JournalNew England Journal of Medicine
Volume298
Issue number9
DOIs
StatePublished - Mar 2 1978

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