DIAMOND-BLACKFAN ANEMIA - A CONGENITAL DEFECT IN ERYTHROPOIESIS

Diamond-Blackfan anemia (DBA) is a congenital pure red blood cell apla sia diagnosed in the first year of life. Familiarity is apparent in 10 % of patients, with all other cases being sporadic. Physical abnormali ties are present in at least one third of patients, pointing to a defe ct in early embryo development. The main clinical sign is profound iso lated anemia, with normal numbers and functioning of the other hemopoi etic cells. Reticulocyte counts are very low. Bone marrow reflects def ective erythropoiesis, showing a very low number of erythropoietic pre cursors and a reduction of BFU-E progenitor cells. Proliferation and d ifferentiation of the other lineages are normal. The very high erythro poietin (EPO) levels are usually not proportionate to the level of ane mia and reflect relative EPO insensitivity, which is also apparent in vitro. Conversely, erythroid progenitors from DBA patients also show a defective or incomplete response to other erythropoietic growth facto rs, such as IL-3 or IL-6. A significant response has been observed in vitro to stem cell factor in many, but not all patients. Many patients respond clinically to corticosteroids and some develop hematologic re missions, both after corticosteroids and spontaneously. Patients who d o not respond to corticosteroids and those who have to discontinue tre atment because of side effects must rely on chronic transfusion and ar e thus exposed to all its complications. Bone marrow transplantation h as been performed in some individuals, usually with a successful outco me. This suggests a normal marrow microenvironment and rules out the h ypothesis of defective stromal cell function. The variable clinical an d biological patterns may be the expression of multiple etiologies or represent variable expressivity of a single genetic defect. Only ident ification of the responsible gene(s) will solve this question. Growth factors exerting an effect on erythropoiesis (and relative receptors) or transacting proteins which regulate their expression are likely can didates in the hunt for a causal gene.