Diamond‐Blackfan anaemia in the U.K.: analysis of 80 cases from a 20‐year birth cohort

Abstract

The U.K. Diamond-Blackfan Anaemia (DBA) Registry was established with the aim of providing a representative database for studies on the aetiology, pathophysiology and treatment of DBA. We have analysed retrospective data from 80 cases (33 male, 47 female) born in the U.K. in a 20-year period (1975-94), representing an annual incidence of 5 per million live births. Ten children from seven families had an apparently familial disorder. 13% were anaemic at birth, and 72.5% had presented by the age of 3 months. 67% had macrocytosis at presentation. 72% responded initially to steroids, and at the time of study 61% were transfusion-independent (45% steroid-dependent) and 39% required regular transfusions. Unequivocal physical anomalies, predominantly craniofacial, were present in 37%, and were more likely in boys (52%) than girls (25%). 18% had thumb abnormalities. Height was below the third centile for age in 28%, and 31% had neither short stature nor physical anomalies. Four children without physical abnormalities had normal red cell indices, and achieved steroid-independent remission, suggesting transient erythroblastopenia of childhood rather than DBA. The birth month distribution of children with sporadic DBA and craniofacial dysmorphism showed a possible seasonality, consistent with a viral aetiology.

RPS19 mutations in patients with Diamond-Blackfan anemia

“…While this is still true, it is now clear that poor steroid sensitivity is common to all patients with RPS19 alterations. Their response to the first steroid course is 46% (42/91 patients whose data were available, two of them showing a partial response) compared with more than 70% of the overall DBA population [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Over the last 10 years, clinical data from the main European and North American DBA registries have been published [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006].…”

“…Their response to the first steroid course is 46% (42/91 patients whose data were available, two of them showing a partial response) compared with more than 70% of the overall DBA population [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Over the last 10 years, clinical data from the main European and North American DBA registries have been published [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Our review of these reports with data for over 800 DBA patients has shown that those with RPS19 mutations display a significantly lower sensitivity to steroids (po0.0001) and are significantly more likely to become transfusion dependent or require SCT (po0.0001) ( Table 2).…”

“…a Complete clinical data were not available for all patients. The range refers to di¡erent values from the di¡erent registries [Ball et al, 1996;Willig et al,1999b;Campagnoli et al, 2004;Lipton et al, 2006]. c Mean age in RPS19 mutated patients 2.573 months (mean age in patients with no RPS19 mutation from the Italian Registry, 5.978 months).…”

“…If our data are confirmed, this definition will be not only important for diagnosis, but may also be relevant for prognosis and perhaps for patienttailored treatment. Ã DBA patient data from the DBA Registries of the United States/Canada, France/Germany, UK, and Italy [Ball et al,1996;Willig et al,1999b;Campagnoli et al, 2004;Lipton et al, 2006]. a Complete clinical data were not available for all patients.…”

“…DBA is primarily treated with steroids and more than 70% of patients respond to the first course [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. The longterm response, however, is extremely variable: some patients go into remission, others develop steroid-resistance.…”