A new type of transfusion-dependent congenital dyserythropoietic anemia

Abstract

A new type of transfusion-dependent congenital dyserythropoietic anemiaCases of congenital dyserythropoietic anemia (CDA) that do not conform to any of the three classical types often present diagnostic difficulties and are at risk of developing secondary hemochromatosis. Here, we report a case of a six year old boy with transfusion dependency and gross abnormalities of the erythroblasts. Haematologica 2007; 92:1427 92: -1428 Case 484/01 of the German Registry of Congenital Dyserythropoietic anemias, male, is the only child of healthy, non-consanguineous German parents. Birth weight was 3,750 g, and there are no dysmorphologies. Scleral icterus and pallor was first noticed at the age of two months. Lowest hemoglobin concentration was 5.4 g/dL, with an MCV of 89 fL and a reticulocyte count of 1.4%. No splenomegaly was noted at the most recent examination at the age of six years. Regular red cell transfusions were given at monthly intervals which ensured a target hemoglobin concentration between 7-12 g /dL. Serum ferritin reached 1,850 ng/mL at the age of 3 years. Non-invasive estimation by superconducting quantum interference device biomagnetometry (SQUID) showed a greatly increased liver iron.Bone marrow aspiration at the age of five months showed increased cellularity, with greatly increased numbers of erythroblasts. Granulocytic cells and megakaryocytes did not show any abnormalities. About 65% of the early and late polychromatic erythroblasts and some more mature basophilic erythroblasts showed distinct dyserythropoietic changes (Figure 1). These include irregular nuclear outlines, formation of nuclear blebs and Howell-Jolly bodies, karyorrhexis, as well as small clear areas and clefts in the nucleus. Five percent of mature cells were bi-or tri-nucleate. Coarse basophilic stippling and large cytoplasmic vacuoles often associated with the nuclear membrane were seen in some cells. Identical aberrations were seen in subsequent marrow aspirates. At the age of six years, storage iron was greatly increased. Ringed sideroblasts were absent.Electron microscopy showed multiple long stretches of double membranes within the cytoplasm, but neither close to or parallel to the cell membrane as in CDA type II. Parts of these membranes were dilated, forming large cytoplasmic vacuoles. Nuclear abnormalities consisted of multiple long intranuclear clefts, dilation of the space between the two layers of the nuclear membrane, loss of parts of the nuclear membrane, duplication, sometimes repeatedly, of stretches of the nuclear membrane, and irregular nuclear outlines ( Figure 2). In some sections, the nuclear membrane was continuous with the cytoplasmic membranes or large cytoplasmic vacuoles.Serum concentration of vitamin B 12 was initially decreased (102 ng/L; reference range 200-900 ng/L) but normal on subsequent controls. Repeated treatment with hydroxycobalamin had no effect on reticulocyte count, hemoglobin concentration or transfusion requirements. Serum vitamin B 12 binding and transcobalamin II serum concentration were n...

Congenital dyserythropoietic anemias: molecular insights and diagnostic approach

“…2 Nevertheless, there were still descriptions of patients not belonging to any of the groups, 2,36,37 suggesting further that CDA subtypes are extremely heterogeneous and probably represent multiple unrelated genetic disorders. Indeed, in recent years additional genetic defects associated with CDA phenotypes have been identified.…”

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

“…The classification scheme originally outlined by Heimpel and Wendt in 1968 is still in use today, subcategorizing the CDAs as Type I, Type II, and Type III [2,3]. Various proposed new subtypes have also been published [4][5][6].…”