Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference

Abstract

SummaryDiamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference.

Hematopoietic defects in rps29 mutant zebrafish depend upon p53 activation

“…Diamond Blackfan anemia (DBA) is a rare, congenital anemia often diagnosed by one year of age[1]. Patients with DBA have a block in erythropoiesis, and often have craniofacial anomalies.…”

The evolving spectrum of ‘non‐classical’ Diamond‐Blackfan anaemia – a case of eADA positive pancytopenia in a young adult

“…In their timely review, Vlachos et al (2008) provided a nuanced picture of the challenges involved in the diagnosis of DiamondBlackfan Anaemia (DBA) and touched on 'non-classical' cases. Arguably, from a diagnostic viewpoint these particular instances are of greatest relevance to most haematologists and we believe the topic deserves greater emphasis.…”

“…In spite of her age, absent overt family history and a pancytopenic presentation, our patient's relatively well preserved marrow cellularity, macrocytosis and a hypothenar flexion deformity prompted us to consider evaluation for DBA. Measurement of eADA is considered a reasonably reliable indicator of DBA and a minor diagnostic criterion in DBA (Orfali et al, 2004;Vlachos et al, 2008), whereas the incidence of eADA elevation in severe aplastic anaemia (SAA) has not been studied to date. In addition to the unusual presentation of non-classical DBA in a young adult, this case is distinguished by progressive pancytopenia (not currently considered a diagnostic criteria for DBA; Diamond et al, 1976) that, unlike reported cases of trilineage haematopoietic defects in DBA, preceded treatment, (Giri et al, 2000).…”

Anémie de Diamond-Blackfan

“…< d'une greffe qui, en France, est proposée dans les formes graves dépendantes de transfusions, ou les formes compliquées. Un article de consensus sur le diagnostic et le traitement de l'ADB a été récemment publié par une communauté internationale de cliniciens [7]. L'ADB est liée à un défaut intrinsèque des progéniteurs érythroïdes et non pas du stroma médullaire, comme l'indiquent à la fois des données in vitro et le succès curatif des greffes de moelle.…”

“…La cartographie pangénomique des SNP (single nucleotide polymorphisms) réalisée dans 215 familles a révélé d'autres locus en lien avec l'ADB : une région de 18 Mb sur le chromosome 8 (8p23. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] et des régions plus petites sur les chromosomes 6 et 10. Concernant le chromosome 10, le séquençage du gène codant la protéine ribosomique RPS24 a mis en évidence chez trois patients deux mutations non-sens et une délétion de la région codante, absentes lors de l'analyse de 200 génomes contrôles [15].…”