Pancytopenia due to decreased intestinal absorption of folate has been well described. In contrast megaloblastic anemia due to blocked cellular folate uptake has not been previously documented. A young man with extensive family history of anemia, pancytopenia and leukemia developed severe pancytopenia. An initially hypercellular bone marrow became markedly hypocellular, and he required 5-15 transfusions monthly for 1 yr because of aplasia and bleeding. Megaloblastic changes gradually became evident and high dose folate therapy was initiated. Despite consistently high serum folate (14-67 ng/ml) and normal serum B12 levels, red cell folate remained low for 2 yr. This disparity suggested defective cellular folate transport. Multiple assays of C14 methyltetrahydrofolate (MTHF) uptake by both his stimulated lymphocytes and marrow cells demonstrated marked impermeability compared to 10 normals (p<0.01). Once loaded by high folate doses, these cells utilized the vitamin normally as measured by deoxyuridine suppression of C14 thymidine uptake. An inhibitor was excluded by cross incubation of normal cells in his serum. These results indicate a defect in folate uptake, possibly of a membrane receptor or carrier, contributed to this patient's aplasia. Consistent with this, after prolonged very high dose folate therapy, his hemoglobin stabilized at 13 gm without tranfusion for 1.3 yr, and his leukocyte and platelet counts rose from 1000 to 4000 and 4000 to 100,000 respectively. The strongly positive family history and the incomplete response to massive folate therapy suggest the defect may be a genetically induced abnormality in cellular folate transport. These techniques should uncover other megaloblastic patients with folate membrane transport or utilization defects.
|Original language||English (US)|
|State||Published - Jan 1 1975|