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Congenital dyserythropoietic anemia type II
Congenital dyserythropoietic anemia type II (CDA II) is the most common form of CDA (see this term) characterized by anemia, jaundice and splenomegaly and often leading to liver iron overload and gallstones.
ORPHA:98873Classification level: Disorder
- CDA II
- CDA type 2
- CDA type II
- Congenital dyserythropoietic anemia type 2
- Hereditary erythroblastic multinuclearity with a positive acidified-serum test (hempas)
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Childhood
- ICD-10: D64.4
- OMIM: 224100
- UMLS: C1306589
- MeSH: -
- GARD: 2001
- MedDRA: -
The prevalence is unknown. Over a 42 year period (1967-2009), 367 CDA II cases were reported in Europe.
The disease usually presents with jaundice and normocytic anemia (mild to severe) in neonates but in some cases symptoms may be so mild that diagnosis can be delayed until adulthood. Splenomegaly and hepatomegaly are also frequent manifestations. Less commonly, posterior mediastinal or paravertebral masses (that consist of extramedullary hemopoietic tissue) are present. In rare cases, hydrops fetalis (see this term) has been associated with CDA II. Long-term complications include secondary hemochromatosis that, if left untreated, can lead to organ damage.
Most cases of CDA II are caused by mutations in the SEC23B gene (20p11.23), coding for a coating protein involved in the reticulum-Golgi trafficking.
Diagnosis of CDA II is based on the presence of congenital anemia, 10-50% binuclearity of bone marrow erythroblasts and increased ferritin levels. Further diagnostic findings include a positive serum acidification (Ham) test, a SDS-PAGE red blood cell (RBC) membrane electrophoresis that reveals a narrow and fast migrating band 3 and a bone marrow electron microscope that reveals the presence of a double membrane in RBC precursors. Molecular genetic analysis can also be used to identify a SEC23B mutation.
The diagnosis of CDA should be considered following exclusion of other causes of hemolytic anemias (especially hereditary spherocytosis), acquired dyserythropoiesis (myelodysplastic syndromes, acute erythroid leukemia) and microcytic anemias (thalassemias or iron deficiency anemias) (see these terms). Gilbert syndrome (see this term) and infections should be also excluded.
Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family.
CDA II is inherited in an autosomal recessive manner and genetic counseling is possible.
Management and treatment
Treatment chosen depends on disease severity and age of patients. Neonates may require an erythrocyte transfusion and in severe cases may be transfusion-dependent for years to come. This need usually diminishes in adolescence and adulthood except under certain circumstances (pregnancy, aplastic crisis, major operations and infections). Hydrops fetalis-associated anemia can be treated with intrauterine transfusions. Vitamin B12 and folic acid supplements are frequently used, although without any evidence of efficacy. The use of erythropoietin formulations also appears to be ineffective. Allogenic bone marrow transplantation has been successful in a few severe cases. Cholecystectomy is often suggested for treatment of cholethiasis. Transfusions can worsen the problem of iron loading and ferritin levels should be monitored annually. Body iron overload can also be monitored by magnetic resonance imaging. Phlebotomies can decrease ferritin concentrations but as they are not well tolerated by some, they should be accompanied by oral chelating agents.
The prognosis of CDA II is usually good. However, morbidity may be important due to iron overload complications that can be fatal if untreated.
A summary on this disease is available in Deutsch (2013) Español (2013) Français (2013) Italiano (2013) Nederlands (2013) Polski (2013, pdf) Polski (2013)
Disease review articles
- Review article
- English (2012) - Haematologica
- Guidance for genetic testing
- Français (2019, pdf) - ANPGM
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