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

Abstract

Congenital dyserythropoietic anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions.

Figure 1.

Flow diagram for differential diagnosis of CDAs. This diagram shows the main steps that allow the differential diagnosis of CDA subtypes among the hypoproliferative anemias, based on clinical, biochemical and molecular findings. The key stages to the diagnosis of CDAs are highlighted in dark blue. CBC: complete blood count; BMF: bone marrow failure; FA: Fanconi's anemia; AA: aplastic anemia; PNH: paroxysmal nocturnal hemoglobinuria; MDS: myelodysplastic syndromes; DBA: Diamond-Blackfan anemia.

Figure 2.

Hematologic parameters in CDA type I and II. The histograms show hemoglobin values, mean cell volume (MCV) and absolute reticulocyte count in CDA type I and II patients. The number of patients enrolled in each comparison is indicated in brackets. Student's t-test was used to compare differences between two groups.

Figure 3.

Distribution of CDAN1 and SEC23B mutations. The pie chart shows the distribution of the different types of mutations found to date in CDAN1 and SEC23B genes (between 2002 and 2012).