Natural history of congenital dyserythropoietic anemia type II

Congenital dyserythropoietic anemia type II (CDA-II) is an autosomal recessive disease characterized by anemia, jaundice, splenomegaly, and erythroblast multinuclearity. The natural history of the disease is unknown. The frequency, the relevance of complications, and the use of splenectomy are poorly defined. This study examined 98 patients from unrelated families enrolled in the International Registry of CDA-II. Retrospective data were obtained using an appropriate questionnaire. The mean age at presentation was 5.2 +/- 6.1 years. Anemia was present in 66% and jaundice in 53.4% of cases. The mean age at correct diagnosis was 15.9 +/- 11.8 years. Twenty-three percent of patients for whom data were available developed anemia during the neonatal period, and 10 of these individuals required transfusions. Splenectomy produced an increased hemoglobin (P <.001) and a reduced bilirubin level (P =.007) in comparison with values before splenectomy. Preliminary data indicate that iron overload occurs irrespective of the hemochromatosis genotype. (Blood. 2001;98:1258-1260)     

Piebaldism associated with congenital dyserythropoietic anemia type II (HEMPAS)

Congenital dyserythropoietic anemias (CDAs) are a group of relatively rare inherited anemias. They are characterized by ineffective erythropoiesis and classified as three major groups and a number of variants. CDA type II, also known as hereditary erythroblastic multinuclearity with a positive acidified serum test (HEMPAS), is the most frequent one. A number of associations with CDA II have been reported, although each described only one or a few patients. Here we presented a piebald woman with vaginal atresia who was tested for anemia and diagnosed as CDA type II. Piebaldism and anemia association were previously described in the mouse. Our case was the first that shows the features of both piebaldism and CDA in the same patient. This association may suggest a stem cell defect to cause both hematopoietic and cutaneous manifestations.     

Paravertebral extramedullary hematopoiesis associated with improvement of anemia in congenital dyserythropoietic anemia type II

Thoracic masses resulting from extramedullary hematopoiesis developed in two sisters of Moroccan origin with congenital dyserythropoietic anemia type II (HEMPAS). In one patient, the diagnosis of extramedullary hematopoiesis was confirmed histologically. The appearance of extramedullary foci of hematopoiesis mimicking mediastinal tumors has not been previously described in HEMPAS. These masses result from persistent erythropoietic stimulation associated with chronic hemolytic anemia. In both patients, detection of the asymptomatic masses was preceded by normalization of hemoglobin levels. Thus unexpected correction of a chronic refractory anemia associated with the appearance of mediastinal masses might be the heralding manifestation of an effective extramedullary hemopoiesis.     

A new type of transfusion-dependent congenital dyserythropoietic anemia

Cases 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.     

A case of congenital dyserythropoietic anemia type II associated with hemochromatosis.

A 54-year-old woman with anemia, diabetes mellitus and liver dysfunction was admitted to our hospital. Numerous binucleated erythroblasts in the bone marrow, a positive serum acidified test, and the presence of anti I and anti i antigens on the surface of her erythrocytes indicated that she had congenital dyserythropoietic anemia (CDA) Type II. Hemochromatosis was confirmed by a liver biopsy. This case is a sibling of a patient with CDA Type II reported by Omine et al in 1981 (Acta Haematol Jpn 44:1). They report that no physical or hematological abnormalities were found when she was examined at the age of 29 years. Twenty-five years later, she developed CDA Type II and hemochromatosis. This case indicates that long-term observation of the family members of a patient with CDA Type II is necessary.     

Proliferation kinetics of bone marrow cells in congenital dyserythropoietic anemia type II

Summary The proliferation kinetics of erythropoiesis and of myelopoiesis have been studied in a case of congenital dyserythropoietic anemia type II (HEMPAS) by means of quantitative 14-C autoradiography, Feulgen cytophotometry and 59-Fe ferrokinetics. Increased total erythropoietic activity and ineffective erythopoiesis was demonstrated by ferrokinetics. Quantitative 14-C autoradiography showed a generally delayed proliferation rate of erythroid cells, most evident in the polychromatic compartment. A deficiency of cell production of 25% was detected among the polychromatic erythroblasts. Part of this fraction is represented by cells still capable of passing to the successive stages of maturation. We conclude that only part of the deficiency of cell production in the polychromatic compartment represents real cell destruction. Most of the measured ineffectiveness is confined to later stages of maturation, such as orthochromatic erthroblasts and marrow reticulocytes.     

Bulky extramedullary hematopoiesis is not a rare complication of congenital dyserythropoietic anemia

Bulky extramedullary hematopoiesis, usually detected in the thorax by imaging techniques, is a well-known complication in many types of congenital anemias. Here, we describe 12 cases of congenital dyserythropoietic anemia with extramedullary hematopoiesis which was always located in the paravertebral space of the thoracic spine and in other paraspinal regions in a few cases. All bulks were originally detected in chest radiographs and confirmed by imaging techniques such as computed tomography and/or magnetic resonance imaging. In some cases, thoracotomy was performed for suspected malignancy. Although the true prevalence is not known, paravertebral masses in patients with CDA of any type are not uncommon and should be the first differential diagnosis considered when masses adjacent to the spine are detected in this disorder.     

Pregnancy outcome in congenital dyserythropoietic anemia type I

Objectives: Congenital dyserythropoietic anemia type I (CDA I) is a rare inherited disease characterized by moderate to severe macrocytic anemia and abnormal erythroid precursors with nuclear chromatin bridges and spongy heterochromatin. Moderate to severe maternal anemia is a recognized independent risk factor for low birth weight (LBW) and complicated delivery. The aim of the study was to review the outcome of pregnancies in women with CDA I. Methods: The clinical and laboratory records of 28 spontaneous pregnancies in six Bedouin women with CDA I were reviewed. The results were compared with findings from a retrospective review of a large population‐based registry including all pregnancies in Bedouin women during the same 15‐yr period. Results: Eighteen pregnancies in women with CDA I (64%) were complicated. One pregnancy was aborted spontaneously in the first trimester and one resulted in a non‐viable fetus (stillborn at 26 wk). Cesarean section (CS) was performed in 10 pregnancies (36%). Eleven of the 26 newborns (42%) had a LBW: six were born prematurely and five were small for gestational age. The odds ratio for CS in women with CDA I compared with healthy Bedouin women was 4.5 [95% confidence interval (CI) 1.2–10.3], and for a LBW infant, 5.5 (95% CI 2.4–12.3). Careful follow‐up was associated with significantly better fetal outcome (P = 0.05). Conclusions: Pregnancies in women with CDA I are at high risk for delivery‐related and outcome complications. To improve fetal outcome, women with CDA I should be carefully monitored during pregnancy.     

Aplastic anemia as a late complication of thymoma in remission

Thymoma has many auto-immune associations, including aplastic anemia and myasthenia gravis. The pathophysiologic relationship between thymoma and its auto-immune sequelae are yet to be fully elucidated, but are thought to be as a result of the production of auto-reactive T cell clones by the thymic epithelium. We report a case in which aplastic anemia did not develop until sometime after remission from thymoma had been induced. This observation suggests that auto-reactive T cells may be produced by the thymoma but not induce clinical auto-immune disease until a later time, even after eradication of thymoma has been achieved.     

An aberrant type of congenital dyserythropoietic anemia associated with a beta-thalassemia trait

Summary A child is described who suffered from a severe congenital anemia. The anemia persisted and a regular transfusional regimen became necessary. Bone marrow aspirates showed an erythroblastic hyperplasia associated with some dyserythropoietic features. A most striking and constant finding was the presence of many intererythroblastic chromatin bridges. The reticulocyte count was always low, in spite of the increased erythropoietic activity. A beta-thalassemia trait inherited from the mother was demonstrated. The hypothesis of dyserythropoiesis/thalassemia syndrome was put forward, based on the assumption that the two genes may have interacted with each other.     

A case of congenital dyserythropoietic anemia type II,Gilbert's syndrome and malleolar trophic ulcers

A case of a woman with congenital dyserythropoietic anemia type II (CDA-II), Gilbert's syndrome (GS) and trophic malleolar ulceration is described. The association of CDA-II and GS caused early gallstone formation that led the patient to undergo cholecystectomy at the age of 15. GS is typified by increased production of both unconjugated and monoconjugated bilirubin, which is more lithogenic. The development of ulcers is not typical of CDA-II, even though they are associated with many of the hemolytic anemias, and were thought in our patient to be due to a thrombophilic tendency which manifest with Antithrombin III and Protein C deficiency.     

Congenital dyserythropoietic anemia type II with a positive sucrose hemolysis test

Hemophagocytic syndrome (HPS) is a rare clinical presentation infrequently associated with lymphoproliferative disorders. We describe a 29-year-old male with aggressive HPS and T-cell lymphoma managed successfully with high-dose chemotherapy and autologous peripheral stem cell transplantation (APSCT), in remission at 41 months of follow-up. In reviewing the literature, this case illustrates the 2nd longest surviving individual post stem cell transplant for aggressive HPS.