A Comprehensive Study of the Neonatal Manifestations of Congenital Dyserythropoietic Anemia Type I

Abstract

Congenital dyserythropoietic anemia (CDA) type I is an inherited disorder characterized by macrocytic anemia with pathognomonic morphologic ultrastructural features of the erythroid precursors. The authors recently cloned the CDAN1 gene and identified one founder missense mutation in all of their Bedouin patients. In a previous study, the authors found that the majority of their 31 Bedouin patients had anemia and jaundice during the first month of life and required blood transfusions; some had persistent pulmonary hypertension. In the present retrospective evaluation of 70 Bedouin patients with CDA type I, the authors more than doubled the number. Forty-five (64%) patients were symptomatic in the neonatal period, 29 (65%) had hepatomegaly, 24 (53%) had early jaundice, 11 (27%) were born small for gestational age, 7 (15%) had persistent pulmonary hypertension, and 6 (13%) had direct hyperbilirubinemia and another 6 (13%) had transient thrombocytopenia. Thirty-six of the symptomatic neonates (80%) required at least one blood transfusion. These results confirm the authors' previous findings and add neonatal manifestations not previously described, particularly hyperbilirubinemia and thrombocytopenia. Early diagnosis of CDA type I may be beneficial in light of the potential efficacy of alpha-interferon in avoiding transfusions in some patients.

Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation

“…Similar observations have been made by others, 29,30 and 17 of 31 patients of Bedouin tribe members were symptomatic in the newborn period. 8 On the other hand, one patient (UPN 409/04) showed macrocytosis without anemia, whereas his sister had moderately low hemoglobin values between 100 and 120 g/L (10-12 g/dL) documented for 30 years. Only 3 cases with borderline anemia were described previously.…”

“…4,5 Seventyseven cases from 68 families have been published as case reports, including 9 of 21 confirmed cases of CDA I collated in the German CDA registry. In addition, there are 70 more cases in the large Bedouin tribe described by Tamary et al 6,7 and Shalev et al 8 from Israel in 1996. CDA I is characterized by congenital anemia, ineffective erythropoiesis, and characteristic morphologic abnormalities on both light and electron microscopy.…”

“…13 Clinical characteristics, complications, and problems of therapy are contained in case reports only, except for studies on the founder population of 45 children or young adults from the 4 extended Bedouin tribes from Israel. 8,14 Here we report epidemiologic data, clinical manifestations, and the course of the disease in 21 patients from 19 unrelated families followed up by one of the authors. Mutations of the CDAN1 gene were investigated in all 16 patients who were alive at the time of analysis.…”

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

“…Most CDA patients have only mild or moderate anemia and do not require medical intervention. About 50% and 10% of neonates with CDA I 45 and CDA II, 46 respectively, need at least one erythrocyte transfusion, and some remain transfusion-dependent in the following years. In most adolescents and adults, the need for transfusions is limited to aplastic crises, pregnancy, severe infections or major operations.…”

Hereditary red cell membrane disorders and laboratory diagnostic testing

“…The identification of genes responsible for type I and type II of congenital dyserythropoietic anemia (CDA)(7) has allowed confirmation of their diagnoses in addition to electron microscopic examination of the erythroblasts in the bone marrow (8,9). Research into hereditary stomatocytoses (Figure 1b) has revealed the involvement of very different transmembrane proteins localized to the lipid bilayer (10)(11)(12), and the molecular basis of monovalent cation transport in this group of rare red cell disorders (13,14).…”