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Diamond-Blackfan Anemia (DBA) is a rare, congenital hypoplastic anemia often diagnosed early in infancy. A moderate to severe aregenerative anemia is found in association with erythroblastopenia in an otherwise normocellular bone marrow. In 40% of these infants with DBA, diverse developmental abnormalities are also noted. A majority of patients with DBA respond to steroid therapy. Recent molecular studies have identified mutations in the gene encoding the ribosomal protein RPS19 on chromosome 19 in 25% of patients with DBA. In another subset of patients, linkage analysis has identified another locus on chromosome 8p in association with DBA. There are, however, other cases of DBA that are linked neither to the RPS19 gene nor to the locus on 8p, implying the involvement of yet-to-be-defined genetic defects in the cause of DBA. The pathogenesis of DBA is still to be fully defined and it is anticipated that further molecular studies will lead to a better understanding of this complex disease.

Diamond-Blackfan anemia, although rare, has been the focus of much attention with respect to both its clinical features and the characterization of the in vitro erythroid defect. Despite this, its pathophysiology is still unclear, and the treatment of steroid-refractory patients is still unsatisfactory. The recent chromosomal localization of a gene for familial Diamond-Blackfan anemia represents an important step forward toward the elucidation of this disorder. Therapeutic advances will depend on the development of collaborative studies, employing consensus criteria for diagnosis and response to therapy.

Until recently, it had been thought that Fanconi anemia patients were distributed into five complementation groups. However, evidence now points to the existence of three new complementation groups, making the genetic basis of the disease more complicated than anticipated. Also, during the past year, the cloning of a second Fanconi anemia gene by both functional complementation and positional cloning has accelerated research of this disease. Although two genes of the eight characterized complementation groups have now been cloned, the function of their gene products still needs to be identified.

Bone marrow failure in the pediatric patient places the hematologist at the junction of clinical medicine, cellular biology, and molecular genetics. The pathophysiology of these disorders is rapidly being elucidated in many laboratories. Treatments such as bone marrow transplantation and the nascent modality of gene therapy are firmly grounded in these modern sciences. This year's progress in the understanding, diagnosis, and treatment of a wide variety of predominantly pediatric bone marrow failure states is a direct result of the union between the "laboratory bench and the patient bedside."