Disease Profile

Congenital dyserythropoietic anemia type 2

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Childhood

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ICD-10

D64.4

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

CDAN2; Anemia, dyserythropoietic, congenital type 2; CDA II;

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders

Summary

Congenital dyserythropoietic anemia type 2 (CDA II) is an inherited blood disorder characterized by mild to severe anemia. It is usually diagnosed in adolescence or early adulthood. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly) and gallstones. This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type II have mediastinal tumors. CDA type II usually results from mutations in the SEC23B gene. It is inherited in an autosomal recessive pattern. Treatment depends on the severity of the symptoms and may involve blood transfusions, iron chelation therapy and removal of the spleen and gallbladder.[1][2]

Symptoms

The signs and symptoms of CDA II include jaundice, gallstones and an enlarged liver and spleen. This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type II have mediastinal tumors. During pregnancy and other special circumstances (such as anemic crisis, major surgery and infections), blood transfusions may be necessary.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Anemia of inadequate production
0010972
Autosomal recessive inheritance
0000007
Cholelithiasis
Gallstones
0001081
Endopolyploidy on chromosome studies of bone marrow
0003352
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Reduced level of N-acetylglucosaminyltransferase II
0003655
Reticulocytosis
Increased immature red blood cells
Increased number of immature red blood cells

[ more ]

0001923
Splenomegaly
Increased spleen size
0001744

Treatment

The goal of CDA type 2 treatment is to address and prevent complications from anemia and iron overload.[3] Most people with CDA type 2 develop iron overload, for some this is as early as in their 20's.[3] If a person with CDA type 2 has mild anemia, but evidence of iron loading, treatment may involve phlebotomy.[3] An alternative treatment is chelation therapy.[3][4] In particular, chelation therapy is preferred for people with iron (ferritin) levels greater than 1000 mg/L.[3] The Iron Disorders Institute provides information on chelation therapy through their Web site at:
https://www.irondisorders.org/chelation-therapy

Many people with CDA-2 maintain hemoglobin levels just above the threshold for symptoms.[4] Mild anemia may not need treatment, as long as it doesn't worsen. Less commonly CDA-2 causes severe anemia. Treatment of severe anemia may involve blood transfusions. Blood transfusions can raise iron levels so, careful monitoring and treatment for iron overload is required.

The National Heart, Lung, and Blood Institute offers tips for living with hemolytic anemia at the following link:
https://www.nhlbi.nih.gov/health/health-topics/topics/ha/livingwith

Splenectomy is considered for people with CDA-2 and severe anemia. Splenectomy can cause a consistent rise in hemoglobin values.[3] The spleen, however, is important in fighting infection. People, particularly children, who have had a splenectomy are more likely to contract a serious and possibly life-threatening infection (sepsis). This risk must be carefully weighed. Splenectomy does not affect iron overload.

Lastly, people with very severe CDA-2 may be candidates for hematopoietic stem cell transplantation (HSCT). Currently this is the only available curative treatment for CDA-2.[3][4][5][6]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn More

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Congenital dyserythropoietic anemia type 2. This website is maintained by the National Library of Medicine.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital dyserythropoietic anemia type 2. Click on the link to view a sample search on this topic.

        References

        1. Congenital dyserythropoietic anemia. Genetics Home Reference (GHR). July 2009; https://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia.
        2. Fernandez, M. Congenital dyserythropoietic anemia type II. Orphanet. September 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=98873.
        3. Renella R, Wood WG. The congenital dyserythropoietic anemias. Hematol Oncol Clin North Am. 2009 Apr; 23(2):283-306. Accessed 6/25/2015.
        4. Renella R. Progress in the congenital dyserythropoietic anemias: juicy but high-hanging fruits?. Am J Hematol. 2010 Dec; 85(12):913-4. Accessed 6/25/2015.
        5. Unal S. Successful hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia type II. Pediatr Transplant. 2014 Jun; 18(4):E130-3. Accessed 6/25/2015.
        6. Braun M. Successful treatment of an infant with CDA type II by intrauterine transfusions and postnatal stem cell transplantation. Pediatr Blood Cancer. 2014 Apr; 61(4):743-5. Accessed 6/25/2015.