Diamond Blackfan anemia: a disorder of red blood cell development.

Diamond Blackfan anemia (DBA) is an inherited hypoplastic anemia that typically presents in the first year of life. The genes identified to date that are mutated in DBA encode ribosomal proteins, and in these cases ribosomal protein haploinsufficiency gives rise to the disease. The developmental timing of DBA presentation suggests that the changes in red blood cell production that occur around the time of birth trigger a pathophysiological mechanism, likely linked to defective ribosome synthesis, which precipitates the hematopoietic phenotype. Variable presentation of other clinical phenotypes in DBA patients indicates that other developmental pathways may also be affected by ribosomal protein haploinsufficiency and that the involvement of these pathways is influenced by modifier genes. Understanding the molecular basis for the developmental timing of DBA presentation promises to shed light on a number of baffling features of this disease. This chapter also attempts to demonstrate how the marriage of laboratory and clinical science may enhance each and permit insights into human disease that neither alone can accomplish.