Frequency of congenital dyserythropoietic anemias in Europe

Abstract

Congenital dyserythropoietic anemia (CDA) was first described in 1967. Soon after the first reports, it became evident that different types exist (1), which share ineffective erythropoiesis as the main mechanism of the anemia and which are all characterized by morphological abnormalities of the erythroblasts, but which are of distinct phenotype and genotype. Specific diagnostic data were first reported from indigenous populations and from AbstractCongenital dyserythropoietic anemias (CDAs) are rare hereditary disorders characterized by ineffective erythropoiesis and striking abnormalities of erythroblast morphology. The mutated genes are known for the most frequent types, CDA I and II, but data about their frequency do not exist. The objective of this retrospective study was to estimate the frequency of CDA I and II, based on all cases reported in the last 42 yr in publications and identified registries or surveys. Reports were collected of 124 and 377 confirmed cases of CDA I and CDA II cases, respectively. The cumulated incidence of both types combined varied widely between European regions, with minimal values of 0.08 cases ⁄ million in Scandinavia and 2.60 cases ⁄ million in Italy. CDA II is more frequent than CDA I, with an overall ratio of approximately 3.2, but the ratio also varied between different regions. The most likely explanations for the differences are both differences in the availability of advanced diagnostic procedures and different levels of the awareness for the diagnosis of the CDAs. The estimations reported here are most probably below the true incidence rates, because of failure to make the correct diagnosis and to underreporting. Limited data do not suggest differing levels of risk in identified ethnic groups.

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

“…13 The wide variation in CDA incidence among European regions could be due to genetic reasons and also to the presence of reference centers with advanced diagnostic procedures available for the diagnosis of CDAs. 10 The true frequency of CDA types I and II is most probably higher than that estimated. This could be due to clinical heterogeneity and diagnostic difficulties, as demonstrated by the observation that in these congenital diseases the correct diagnosis is often delayed until adulthood.…”

“…Furthermore, in many families there is only one single affected individual, which makes determination of the inheritance pattern very difficult. Indeed recessive inheritance, de novo mutation and low expression alleles are difficult 10,15 Although CDA II patients are to be found right across the Italian peninsula, the majority of ancestors came from Southern Italy, where a founder effect has been observed. 13 The wide variation in CDA incidence among European regions could be due to genetic reasons and also to the presence of reference centers with advanced diagnostic procedures available for the diagnosis of CDAs.…”

Congenital dyserythropoietic anemia type II (CDA II) diagnosed in an adult patient

“…It is the most widely documented subtype of CDA, with approximately 367 cases reported in the literature, predominantly in European populations [15]. The term HEMPAS derives from observations by Crookston et al that the red blood cells from CDA II patients demonstrated susceptibility to lysis in ABO-compatible normal sera in the acidified serum lysis test (HAM's test) [16].…”

Inherited hematological disorders due to defects in coat protein (COP)II complex

“…The prevalence of CDAs in Europe has been recently assessed [52]. After this evaluation, CDA II seems to be the most frequent form of CDAs.…”