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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Dihydrofolate reductase deficiency causing megaloblastic anemia in two families.

To determine the cause of severe megaloblastosis detected at birth and at four weeks in two unrelated infants their bone marrow and liver cells were studied. Both patients had abnormal deoxyuridine suppression tests, corrected to normal by 5-formyl tetrahydrofolic acid. Liver-cell homogenate from one patient had a previously undetectable level of dihydrofolate reductase restored to normal by high cation concentration in the assay. Activity of the liver-cell homogenate from the other patient, which was one quarter of the normal level, was restored to only half normal activity by high cation concentration. Dihydrofolic acid reductase deficiency prevents this conversion of folic acid to tetrahydrofolic acid; the enzyme activity appears to differ in each patient. A satisfactory clinical response in both patients followed parenteral therapy with 5-formyl tetrahydrofolic acid. One sibling in each family died of a similar illness. Autosomal recessive inheritance is probable.[1]


  1. Dihydrofolate reductase deficiency causing megaloblastic anemia in two families. Tauro, G.P., Danks, D.M., Rowe, P.B., Van der Weyden, M.B., Schwarz, M.A., Collins, V.L., Neal, B.W. N. Engl. J. Med. (1976) [Pubmed]
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