Congenital dyserythropoietic anemia

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Congenital dyserythropoietic anemia
Other namesFamilial erythroid multinuclearity, [1] Hereditary Erythroblastic Multinuclearity with a Positive Acidified Serum lysis test (HEMPAS) [2]
Blausen 0761 RedBloodCells.png
Specialty Hematology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Anemia, weakness, tiredness, enlarged spleen, iron overload [3]
Usual onsetFrom birth
TypesTypes 1,2,3 and 4 [4]
Causes Genetic
Diagnostic method Genetic testing [5]
TreatmentBlood transfusion, stem cell transplant [6]

Congenital dyserythropoietic anemia (CDA) is an umbrella term used to denote a group of rare blood disorder s which share some characteristics. All have genetic origin, usually inherited from parents; and they are characterised by a partial failure of the bone marrow to produce healthy red blood cell s. This in turn leads to anemia which in some cases can be severe. [3]

Contents

Symptoms of CDA depend on the type and its severity; they can include tiredness, weakness, and jaundice. In some cases the liver or spleen may become enlarged. CDA may also cause the body to absorb too much iron, leading to damage of other organs. [3] Four types of CDA are generally recognised, designated as CDA-1, CDA-2, CDA-3 and CDA-4. [3] Other variants have been described; each type has a distinct genetic cause and identifiable changes in the bone marrow. [7] Exact diagnosis of the disease requires microscopic examination of a bone marrow sample, followed by genetic sequencing. [7]

Mild cases may need no treatment. Severe cases must be managed by regular blood transfusions; stem cell transplantation from a well matched donor is also possible. [7] As of 2024, fewer than a thousand cases of CDA have been described worldwide; prevalence in Europe is fewer than 1 case per million. [7] [8]

The term congenital dyserythropoietic anemia was first coined in 1968 when three types (CDA-1, CDA-2 and CDA-3) were included in the group. [9]

Types

CDA-1

CDA anemia type 1 presents as moderate to severe macrocytic anemia with symptoms like fatigue, weakness, and pale skin, often presenting in childhood. It is also associated with enlarged spleen and liver. The bone marrow shows abnormal chromatin under the microscope. It is caused by a mutation in the CDAN1 or CDIN1 gene, and has autosomal recessive inheritance. [10] [11] [12]

CDA-2

Features of congenital dyserythropoietic anemia type 2 (CDA II) include enlarged spleen (splenomegaly), jaundice, gallstones, and often iron overload. Under the microscope, the bone marrow shows a high number of erythroblasts with two nuclei. The cause is a mutation in the SEC23B gene, and has autosomal recessive inheritance. [10] [13] It is the most common form of CDA, and is also known as HEMPAS (hereditary erythroblastic multinuclearity with a positive acidified serum test). [14]

CDA-3

This is extremely rare; as of 2025 it has only been found in three families. It is characterized by mild to moderate anemia and the presence of giant erythroblasts in the bone marrow, with multiple nuclei. It can be caused by a mutation in the KIF23 gene (in which case inheritance is autosomal dominant) or the RACGAP1 gene (in which case inheritance is autosomal recessive). The proteins from these genes are essential for the cytokinesis phase of cell division. [15] [3] The first cases of CDA-3 were described in 1951 and initially called "familial erythroid multinuclearity" [16]

CDA-4

This is a moderate to severe anemia which is evident at birth and can potentially be detected during pregnancy. In severe cases, the unborn child may have hydrops fetalis (swelling caused by fluid accumulation before birth). It is extremely rare; only 10 cases have been diagnosed worldwide. In each case, the cause is a mutation of the KLF1 gene, which is necessary for the proper maturation of red blood cells. Unlike types 1-3, this is a de novo mutation which was not inherited. [17] [3] Some authorities regard CDA-4 as one of a subgroup of transcription-factor related CD anemias. [18]

Other types

These include Majeed syndrome and some instances of sideroblastic anemia. [18]

Signs and symptoms

The typical symptoms of anaemia are common to all types of CDA - depending on severity, these can include fatigue, weakness, jaundice, and an enlarged liver and spleen (hepatosplenomegaly). CDA may also cause the body to absorb too much iron, leading to damage to tissues and organs. [3]

Other symptoms are specific to the type of CDA involved. [3] [7]

Diagnosis

Diagnosing CDA involves a bone marrow examination, and genetic testing to confirm the diagnosis and type. Microscopic examination of a bone marrow smear is crucial for identifying specific changes such as erythroblasts with multiple nuclei. Genetic testing is used for final confirmation. [10]

Treatment

Treatment of individuals with CDA usually consist of frequent blood transfusions, but this can vary depending on the type and severity of anemia that the individual has. [6]

See also

References

  1. Liljeholm, Maria; Irvine, Andrew F.; Vikberg, Ann-Louise; Norberg, Anna; Month, Stacy; Sandström, Herbert; Wahlin, Anders; Mishima, Masanori; Golovleva, Irina (2013-06-06). "Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23". Blood. 121 (23): 4791–4799. doi:10.1182/blood-2012-10-461392. ISSN   0006-4971.
  2. Fukuda, Michiko N (1999-10-08). "HEMPAS". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1455 (2): 231–239. doi:10.1016/S0925-4439(99)00070-8. ISSN   0925-4439.
  3. 1 2 3 4 5 6 7 8 "Congenital dyserythropoietic anemia: MedlinePlus Genetics". National Library of Medicine. Retrieved 2025-10-08.
  4. "Orphanet: Congenital dyserythropoietic anemia". www.orpha.net. Archived from the original on 3 January 2018. Retrieved 2 January 2018.
  5. "Congenital dyserythropoietic anemia - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 27 May 2018. Retrieved 2 January 2018.
  6. 1 2 Greer, John P.; Arber, Daniel A.; Glader, Bertil; List, Alan F.; Means, Robert T.; Paraskevas, Frixos; Rodgers, George M. (2013-08-29). Wintrobe's Clinical Hematology. Lippincott Williams & Wilkins. p. 994. ISBN   9781469846224.
  7. 1 2 3 4 5 "Congenital dyserythropoietic anemia". Orphanet: Knowledge on rare diseases and orphan drugs. July 2025. Retrieved 2025-10-08.
  8. Dass, Jasmita; Nayak, Amiya Ranjan; Puri, Vandana; Aggarwal, Mukul (2024-06-01). "Congenital dyserythropoietic anemia in children: Case series with review of literature". Pediatric Hematology Oncology Journal. 9 (2): 55–61. doi:10.1016/j.phoj.2024.02.004. ISSN   2468-1245.
  9. "ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE Ia". Online Mendelian Inheritance in Man. 2 October 2014. Retrieved 13 October 2025.
  10. 1 2 3 Iolascon, Achille; Heimpel, Hermann; Wahlin, Anders; Tamary, Hannah (2013-09-26). "Congenital dyserythropoietic anemias: molecular insights and diagnostic approach". Blood. 122 (13): 2162–2166. doi:10.1182/blood-2013-05-468223. ISSN   0006-4971. PMC   3785118 . PMID   23940284.
  11. "Congenital Dyserythropoietic Anemia (CDA)". Boston Children's Hospital. Retrieved 2025-10-11.
  12. "Orphanet: Congenital dyserythropoietic anemia type I". www.orpha.net. Retrieved 2025-10-11.
  13. "Orphanet: Congenital dyserythropoietic anemia type II". www.orpha.net. Retrieved 2025-10-11.
  14. Alam, Kiran; Aziz, Mehar; Varshney, Manoranjan; Maheshwari, Veena; Basha, Mahfooz; Gaur, Kavita (2011-01-01). "Congenital dyserythropoietic anaemia type II: a rare entity". Case Reports. 2011: bcr0120113684. doi:10.1136/bcr.01.2011.3684. ISSN   1757-790X. PMC   3082060 . PMID   22696622.
  15. "Orphanet: Congenital dyserythropoietic anemia type III". OrphaNet. July 2023. Retrieved 2025-10-13.
  16. Liljeholm, Maria; Irvine, Andrew F.; Vikberg, Ann-Louise; Norberg, Anna; Month, Stacy; Sandström, Herbert; Wahlin, Anders; Mishima, Masanori; Golovleva, Irina (2013-06-06). "Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23". Blood. 121 (23): 4791–4799. doi:10.1182/blood-2012-10-461392. ISSN   0006-4971.
  17. Tallack MR, Perkins AC (December 2010). "KLF1 directly coordinates almost all aspects of terminal erythroid differentiation". IUBMB Life. 62 (12): 886–90. doi:10.1002/iub.404. PMID   21190291. S2CID   10762358.
  18. 1 2 Iolascon, Achille; Andolfo, Immacolata; Russo, Roberta (2020-09-10). "Congenital dyserythropoietic anemias". Blood. 136 (11): 1274–1283. doi:10.1182/blood.2019000948. ISSN   0006-4971.

Further reading