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Diamond-Blackfan Anaemia

An Overview

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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.

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Acknowledgements

The authors wish to thank Professor C. Camaschella for reading the manuscript and her helpful suggestions. The support of the DBA Working Group of the European Society for Paediatric Haematology and Immunology is gratefully acknowledged. The work reported in this article was partially supported by Telethon Italia, project E.619, and by a Ministero Universita’ e Ricerca Scientifica e Tecnologica (MURST) 60% grant.

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Authors and Affiliations

  1. Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy

    Irma Dianzani

  2. Department of Paediatric Sciences, University of Turin, Piazza Polonia 94, 10126, Turin, Italy

    Irma Dianzani, Emanuela Garelli & Ugo Ramenghi

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  1. Irma Dianzani
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Correspondence to Irma Dianzani.

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Dianzani, I., Garelli, E. & Ramenghi, U. Diamond-Blackfan Anaemia. Paediatr Drugs 2, 345–355 (2000). https://doi.org/10.2165/00128072-200002050-00002

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