A case of macrocytosis and megaloblastic erythropoiesis of unknown aetiology

The clinical and laboratory features in a non-anaemic 23-year-old female with marked macrocytosis and florid megaloblastic erythropoiesis of unknown aetiology are described. The bone marrow cells gave a normal deoxyuridine-suppressed value indicating that the megaloblastic erythropoiesis was not caused by vitamin B12 or folate deficiency or an impairment of the methylation of deoxyuridylate due to any other cause. The megaloblastic changes were associated with a marked degree of dyserythropoiesis, the most frequent ultrastructural abnormality being the presence of single or multiple intranuclear clefts. The characteristic light and electron microscope features of type I and type III congenital dyserythropoietic anaemia, in which mild megaloblastic changes may be seen, were absent. The distribution of the erythroblasts in the cell cycle was grossly abnormal and similar to that in severe pernicious anaemia; a high proportion of the cells were in the G2 phase and a substantial proportion seemed to have become arrested after progressing through part of the S phase. The bone marrow macrophages contained phagocytosed erythroblasts indicating that erythropoiesis was ineffective. It seems likely that the primary biochemical defect in the erythroblasts was some congenital disorder of DNA or nucleoprotein synthesis.