An update on the pathogenesis and diagnosis of Diamond–Blackfan anemia

Abstract

Diamond–Blackfan anemia (DBA) is a rare congenital hypoplastic anemia characterized by a block in erythropoiesis at the progenitor stage, although the exact stage at which this occurs remains to be fully defined. DBA presents primarily during infancy with macrocytic anemia and reticulocytopenia with 50% of cases associated with a variety of congenital malformations. DBA is most frequently due to a sporadic mutation (55%) in genes encoding several different ribosomal proteins, although there are many cases where there is a family history of the disease with varying phenotypes. The erythroid tropism of the disease is still a matter of debate for a disease related to a defect in global ribosome biogenesis. Assessment of biological features in conjunction with genetic testing has increased the accuracy of the diagnosis of DBA. However, in certain cases, it continues to be difficult to firmly establish a diagnosis. This review will focus on the diagnosis of DBA along with a description of new advances in our understanding of the pathophysiology and treatment recommendations for DBA.

Spontaneous remission in a Diamond‐Blackfan anaemia patient due to a revertant uniparental disomy ablating a de novo RPS19 mutation

“…Diamond‐Blackfan Anaemia (DBA; Mendelian Inheritance in Man reference 105650) is an inherited bone marrow (BM) failure syndrome that, in most cases, shows onset in the first year of life and is characterized by hyporegenerative anaemia, congenital malformations in about one‐third of patients and elevated erythrocyte adenosine deaminase activity (eADA) (Da Costa et al , ).…”

“…DBA belongs to the large family of ribosomopathies and is usually caused by alterations in one of 20 ribosomal protein (RP) genes that lead to haploinsufficiency (Da Costa et al , ).…”

New insights into red cell rheology and adhesion in patients with sickle cell anaemia during vaso‐occlusive crises

“…DBA belongs to the large family of ribosomopathies and is usually caused by alterations in one of 20 ribosomal protein (RP) genes that lead to haploinsufficiency (Da Costa et al, 2018).…”

Hematopoietic cell transplantation for Diamond Blackfan anemia: A report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society

“…The majority of patients received a cyclophosphamide or busulfan-based myeloablative regimen as recommended. 12,30 Even so, non-myeloablative and reduced-intensity conditioning regimens have been successfully used in small case series, particularly in very Median days to neutrophil engraftment (range) 20 21 19 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) .59…”

“…The presence of an elevated erythrocyte adenosine deaminase (eADA) activity is present in over 75% of cases. [10][11][12][13] Diamond-Blackfan anemia patients have a higher incidence of hematological malignancies (myelodysplastic syndrome and acute myeloid leukemia) and solid tumors, such as colon carcinoma and osteogenic sarcoma osteosarcoma. 14,15 Steroids starting in the second year of life are considered first-line treatment, with an 80% initial response in younger children.…”