4.2 Diamond-Blackfan anaemia (DBA)

DBA (OMIM 105650), is a rare disease with a dominant autosomal inheritance pattern. No differences were observed between men and women (ratio 1:1) and the short stature is the most frequent anomaly followed by alterations in the thumb. Other less frequent anomalies have been described, such as craniofacial alterations, cleft lip, cleft palate and short neck. In DBA, the first description was a pure neonatal anaemia that required transfusion support. At present, about 1000 cases have already been described in the literature, and approximately 25% of them have at least one congenital anomaly. The average age for diagnosis is 3 months, ranging from birth to 64 years of age, with 98% of cases diagnosed in the first year of life. DBA has its molecular basis in heterozygous mutations in the genes encoding the components of either the small 40S or the large 60S ribosomal subunits that affect the processing of ribosomal RNA. Recently, DBA has also been related to mutations in the GATA-1


#### The Rare Anaemias DOI: http://dx.doi.org/10.5772/intechopen.86986


#### Table 3.

Genetic subtypes and genes implicated in Diamond-Blackfan anaemia (DBA).

transcription factor [16], but about 45% of patients with ADB lack mutations in these identified genes, as shown in Table 3. It is likely that the genetic defects in this pathology accelerate the apoptosis of erythroid progenitor cells, since it has been shown that MDM2, a central regulator of p53, that acts as a ubiquitin ligase that leads to the degradation of p53, binds specifically to several free ribosomal proteins. From the clinical point of view, the diagnosis of DBA is complex. Blood counts generally show a macrocytic anaemia with reticulocytopenia, as well as elevated Hb F and RBC adenosine deaminase (ADA) in more than 85% of patients. In the bone marrow, a pure erythroblastopenia without abnormalities in the other haematopoietic cell lines is characteristic. The cumulative incidence for MDS, AML, and some solid tumours (osteosarcoma, Hodgkin's lymphoma) has been estimated at 20% at 46 years, which implies an increased risk of developing cancer. The treatment is based on the response of a large number of patients to steroids. However, it is advised not to perform this treatment until after the first year of age. Until then, and in those patients who do not respond to steroids, or who require them at very high doses, the only treatment will be adequate transfusion support with packed red blood cells. The only curative treatment for the disease is the HSCT, provided the existence of an identical HLA family donor [11].
