Congenital Familial Megaloblastic Anemia

Abstract

Abstract Two sisters with a previously unreported megaloblastic anemia unassociated with a deficiency of either folic acid or vitamin B12 are described. Deficiencies of these vitamins were ruled out by standard studies. All other previously reported forms of megaloblastic anemia not secondary to a vitamin deficiency, such as orotic aciduria, were also excluded by appropriate studies. Optimal hemoglobin responses were obtained after the administration of large amounts of both vitamin B12 and folic acid. Because of this hemoglobin response, the conversion of deoxyuridine-5-monophosphate to deoxythymidine-5-monophosphate in vitro was examined in bone marrow samples from both patients using a modification of a method described by Killmann.18 This preliminary step in DNA synthesis was found to be normal. The results of this test and the optimal hemoglobin response after administration of both vitamins suggest that both folic acid and vitamin B12 may be necessary at some other preliminary step in DNA synthesis.