Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation

Abstract

IntroductionThe congenital dyserythropoietic anemias (CDAs) comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by distinct morphologic abnormalities of the majority of erythroblasts in the bone marrow. The term was first used by Crookston et al 1 (for cases later classified as CDA II) and by Wendt and Heimpel 2 (for cases later classified as CDA I), but a few reports of similar cases had been published previously. 3 In 1968, we proposed classifying these disorders into 3 types. 3 Although initially proposed as a working classification, it was widely accepted and is still used today in clinical practice. 4,5 CDA II, also known as hereditary erythroblastic multinuclearity with a positive acidified-serum test (HEMPAS), 6 is the most frequently encountered disorder of the CDA group. 4,5,7,8 The leading morphologic abnormality is binuclearity or multinuclearity occurring in 10% to 50% of mature erythroblasts, with equal DNA content in both nuclei. 9 Electron microscopy (EM) shows a double membrane close to the cell membrane of mature erythroid cells, 10 which is due to residual endoplasmic reticulum. 11 Band 3 appears thinner and shows faster migration on sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). 12 Red cells of patients with CDA II retain throughout life a very high agglutinability by anti-i sera. 6 The abnormalities of the CDA II red blood cell membrane are due to abnormal processing of N-glycans. 13 Band 3 and band 4.5 glycoproteins carry truncated polylactosamine structures, while glycolipids are sometimes overglycosylated. 14 An association to a gene locus on chromosome 20 (q11.2) was described in families from Southern Italy. 7,15 After our description of the first families in 1968, 3,16 we observed many more cases, mostly in residents of Germany, but also from Austria, Switzerland, and the Czech Republic, and we were able to follow some patients up to 35 years. Data from these patients as well as from case reports in the literature were collected in the German CDA registry, set up in 1993. Here we report epidemiologic data, clinical manifestations, and diagnostic features of 48 patients with CDA II. Particular emphasis is given to the course of the disease as a basis for management of these patients. Patients, materials, and methodsDiagnosis of CDA II was based on the criteria shown in Table 1. Data were extracted from files of the institutions and physicians responsible for patients' management from 1950 to 2002, in addition to the personal observations of one of the authors (H.H.) from the university hospitals of Freiburg and Ulm, Germany. Informed consent was obtained for additional blood samples taken for research objectives. A code identifying the family, the cases, and their relatives was assigned to each individual. Family trees were constructed by Cyrillic 2.1.2 (Cherwell Scientific Publishing, Oxford, United Kingdom). Data from 14 patients from 11 families had been published ...

Congenital Dyserythropoietic Anemia Type 1: Report of One Patient and Analysis of Previously Reported Patients Treated with Interferon Alpha

“…Treatment of CDAs is mostly supportive and includes erythrocyte transfusions and iron chelation. Splenectomy can increase hemoglobin levels and eliminate the need for transfusions in CDA type 2 patients without having a beneficial effect on iron overload [4,12]. Hematopoieitic stem cell transplantation is the only available curative treatment modality and can be considered in transfusion dependent, severe patients with human leukocyte antigenidentical donors [13].…”

The morphological diagnosis of congenital dyserythropoietic anemia: results of a quantitative analysis of peripheral blood and bone marrow cells

“…4,5 Confirmation of the diagnosis of CDA I required a mutation of the CDAN1-gene and/ or typical aberrations seen by electron microscopy. 2,6 Confirmation of the diagnosis of CDA II required a mutation of the SEC23B-gene or at least one of the following parameters: positive acid serum lysis test with ABO-compatible sera, 7 a typical abnormality of band 3 shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 8,9 or a discontinuous double membrane in mature erythroblasts seen by electron microscopy.…”

Congenital dyserythropoietic anemia type II — a case report of two siblings in a family

“…The classifi cation of the congenital dyserythropoietic anemia was originally based on distinct differences in the morphology of the bone marrow erythroblasts [7]. Of the three types, type II is the commonest, identifi ed by positive Ham's test and multinucleated erythroblasts.…”