Diamond-Blackfan Anaemia

Abstract

Diamond Blackfan Anaemia (DBA) is a congenital disease characterised by defective erythroid progenitor maturation. It is usually diagnosed during the first year of life. The main clinical sign is profound isolated normochromic or macrocytic anaemia, with normal numbers and function of the other haemopoietic cells. Reticulocyte counts in patients with DBA are very low. Bone marrow reflects the defective erythropoiesis, showing a very low number of erythropoietic precursors and a reduction of erythroid burst-forming unit progenitor cells. The proliferation and differentiation of the other lineages are normal. More than one-third of patients have malformations, most often involving the upper limbs and head, and the urogenital or cardiovascular systems. However, the link between these malformations and defective erythropoiesis is unclear and a defect in a molecule acting on both early embryonic development and haematopoiesis has been proposed. Whereas most cases are sporadic, inheritance is observed in 10% of patients, with a dominant or, more rarely, recessive pattern. One locus on chromosome 19q13.2 encoding ribosomal protein S19 accounts for a quarter of patients with either the dominant or the sporadic form. Families not linked with this locus have also been described. The diagnosis of DBA may be difficult and differential diagnoses include Fanconi's anaemia and acquired erythroid aplasias. Erythrocyte adenosine deaminase levels are generally high in DBA patients, which may help in the diagnosis, but they are not pathognomic. Corticosteroids are the main treatment option in DBA and these agents induce erythropoiesis in over 60% of patients. Some patients achieve complete remission, which may be either corticosteroid-induced or spontaneous. The increased in vitro erythropoiesis occasionally induced by the addition of specific cytokines, namely interleukin (IL)-3 and stem cell factor (SCF), has suggested their use in vivo. However, few patients have responded to IL-3, whereas SCF administration, though interesting in theory, has not yet been attempted. Patients who do not respond to corticosteroids and those who have to discontinue treatment because of adverse events must rely on long term transfusions, and are thus exposed to all of the associated complications. Bone marrow or cord blood transplantation has been performed in some patients. The former approach is burdened with severe complications and high mortality.

Congenital Aplastic Anemia Caused by Mutations in the SBDS Gene: A Rare Presentation of Shwachman-Diamond Syndrome

“…Congenital BM failures have been characterized primarily as single-lineage failures, as seen in Kostmann syndrome or other variants of severe chronic neutropenia, 16 congenital amegakaryocytic thrombocytopenia or thrombocytopenia with absent radii syndrome, 11,17,18 or DiamondBlackfan anemia. 12 The presentation of SDS for our patient was highly unusual. The SBDS gene product is presumed to function in RNA processing.…”

“…[10][11][12][13][14][15] BM failure syndromes almost always occur in childhood until adulthood, with symptoms related to the predominant cytopenia, and often culminate in multilineage failures with time. Congenital BM failures have been characterized primarily as single-lineage failures, as seen in Kostmann syndrome or other variants of severe chronic neutropenia, 16 congenital amegakaryocytic thrombocytopenia or thrombocytopenia with absent radii syndrome, 11,17,18 or DiamondBlackfan anemia.…”

Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

“…[1][2][3] Current therapies such as steroids, blood transfusion, and bone marrow transplantation often have severe side effects or are ineffective in many DBA patients. 1,[4][5][6][7][8] Approximately 40% of DBA patients have additional abnormalities that include short stature, cranofacial and urogenital malformations, heart defects and mental retardation. 1,8 DBA patients are also predisposed to develop acute myeloid leukemia, lymphoma and solid tumors.…”

“…1,8 DBA patients are also predisposed to develop acute myeloid leukemia, lymphoma and solid tumors. 5,[8][9][10] Approximately 25% of DBA patients have mutations in the gene encoding the S19 ribosomal protein (RPS19), 11,12 which is one of 33 ribosomal proteins that make up the 40S ribosomal subunit that is involved in translation. 13 Down-regulation of RPS19 in CD34 + human hematopoietic stem cells disrupts erythroid progenitor cell but not myeloid cell development, 14,15 which mimics the hematologic features observed in DBA.…”

Anesthetic Management of an Adolescent With Diamond-Blackfan Syndrome During Posterior Spinal Fusion

“…Associated involvement in other end-organs may include craniofacial defects, cardiac pathology, short stature, and skeletal abnormalities including scoliosis [12]. Bone marrow involvement is generally limited to the red cell lineage with a normal leukocyte and platelet count.…”