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Congenital dyserythropoietic anemia

MedGen UID:
8064
Concept ID:
C0002876
Disease or Syndrome
Synonyms: Anemia, Congenital Dyserythropoietic; Anemia, Dyserythropoietic, Congenital; Anemias, Congenital Dyserythropoietic; Congenital Dyserythropoietic Anemia; Congenital Dyserythropoietic Anemias; Dyserythropoietic Anemia, Congenital; Dyserythropoietic Anemias, Congenital
SNOMED CT: CDA - congenital dyserythropoietic anemia (52951008); Congenital dyserythropoietic anemia (52951008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Related genes: CDAN1, CDIN1, KLF1, SEC23B, KIF23, GATA1
 
Monarch Initiative: MONDO:0019403
OMIM® Phenotypic series: PS224120
Orphanet: ORPHA85

Definition

Congenital dyserythropoietic anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This disorder is one of many types of anemia, which is a condition characterized by a shortage of red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and other complications.

Researchers have identified three major types of CDA: type I, type II, and type III. The types have different genetic causes and different but overlapping patterns of signs and symptoms.

CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). 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 I are born with skeletal abnormalities, most often involving the fingers and/or toes.

The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.

The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma).

Several other variants of CDA have been described, although they appear to be rare and not much is known about them. Once researchers discover the genetic causes of these variants, some of them may be grouped with the three major types of CDA. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Abu-Quider A, Asleh M, Shalev H, Fruchtman Y, Ben-Harosh M, Beck G, Kapelushnik J
Eur J Haematol 2020 Aug;105(2):216-222. Epub 2020 May 19 doi: 10.1111/ejh.13428. PMID: 32302424
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Cazzola M, Invernizzi R
Haematologica 2010 May;95(5):693-5. doi: 10.3324/haematol.2009.021683. PMID: 20442439Free PMC Article

Recent clinical studies

Etiology

Iolascon A, Andolfo I, Russo R
Blood 2020 Sep 10;136(11):1274-1283. doi: 10.1182/blood.2019000948. PMID: 32702750
Roy NBA, Babbs C
Br J Haematol 2019 May;185(3):436-449. Epub 2019 Mar 5 doi: 10.1111/bjh.15817. PMID: 30836435Free PMC Article
Ru Y, Liu G, Bai J, Dong S, Nie N, Zhang H, Zhao S, Zheng Y, Zhu X, Nie G, Zhang F, Eyden B
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Kamiya T, Manabe A
Int J Hematol 2010 Oct;92(3):432-8. Epub 2010 Sep 7 doi: 10.1007/s12185-010-0667-9. PMID: 20820969
Wickramasinghe SN
Curr Opin Hematol 2000 Mar;7(2):71-8. doi: 10.1097/00062752-200003000-00001. PMID: 10698292

Diagnosis

Iolascon A, Andolfo I, Russo R
Blood 2020 Sep 10;136(11):1274-1283. doi: 10.1182/blood.2019000948. PMID: 32702750
Roy NBA, Babbs C
Br J Haematol 2019 May;185(3):436-449. Epub 2019 Mar 5 doi: 10.1111/bjh.15817. PMID: 30836435Free PMC Article
Gambale A, Iolascon A, Andolfo I, Russo R
Expert Rev Hematol 2016 Mar;9(3):283-96. Epub 2016 Jan 6 doi: 10.1586/17474086.2016.1131608. PMID: 26653117
Iolascon A, Heimpel H, Wahlin A, Tamary H
Blood 2013 Sep 26;122(13):2162-6. Epub 2013 Aug 12 doi: 10.1182/blood-2013-05-468223. PMID: 23940284Free PMC Article
Iolascon A, Russo R, Delaunay J
Curr Opin Hematol 2011 May;18(3):146-51. doi: 10.1097/MOH.0b013e32834521b0. PMID: 21378561

Therapy

Roy NBA, Babbs C
Br J Haematol 2019 May;185(3):436-449. Epub 2019 Mar 5 doi: 10.1111/bjh.15817. PMID: 30836435Free PMC Article
Rathe M, Møller MB, Greisen PW, Fisker N
Pediatr Blood Cancer 2018 Mar;65(3) Epub 2017 Oct 19 doi: 10.1002/pbc.26866. PMID: 29049846
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Dermatol Clin 2017 Jan;35(1):21-38. doi: 10.1016/j.det.2016.07.005. PMID: 27890235Free PMC Article
Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, Griesshammer A, Marquardt T, Janka-Schaub G, Kron M, Kohne E
Blood 2003 Dec 15;102(13):4576-81. Epub 2003 Aug 21 doi: 10.1182/blood-2003-02-0613. PMID: 12933587
Iancu TC
Mol Aspects Med 1983;6(1):1-100. doi: 10.1016/0098-2997(83)90004-3. PMID: 6371428

Prognosis

Moreno-Carralero MI, Horta-Herrera S, Morado-Arias M, Ricard-Andrés MP, Lemes-Castellano A, Abio-Calvete M, Cedena-Romero MT, González-Fernández FA, Llorente-González L, Periago-Peralta AM, de-la-Iglesia-Íñigo S, Méndez M, Morán-Jiménez MJ
Eur J Haematol 2018 Sep;101(3):368-378. Epub 2018 Jul 27 doi: 10.1111/ejh.13112. PMID: 29901818
Shalev H, Al-Athamen K, Levi I, Levitas A, Tamary H
Eur J Haematol 2017 Jan;98(1):13-18. Epub 2016 Jun 15 doi: 10.1111/ejh.12778. PMID: 27206021
Iolascon A, Russo R, Delaunay J
Curr Opin Hematol 2011 May;18(3):146-51. doi: 10.1097/MOH.0b013e32834521b0. PMID: 21378561
Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, Griesshammer A, Marquardt T, Janka-Schaub G, Kron M, Kohne E
Blood 2003 Dec 15;102(13):4576-81. Epub 2003 Aug 21 doi: 10.1182/blood-2003-02-0613. PMID: 12933587
Wickramasinghe SN
Curr Opin Hematol 2000 Mar;7(2):71-8. doi: 10.1097/00062752-200003000-00001. PMID: 10698292

Clinical prediction guides

Da Costa L, Mohandas N, David-NGuyen L, Platon J, Marie I, O'Donohue MF, Leblanc T, Gleizes PE
Blood Cells Mol Dis 2024 May;106:102838. Epub 2024 Feb 17 doi: 10.1016/j.bcmd.2024.102838. PMID: 38413287
Moreno-Carralero MI, Horta-Herrera S, Morado-Arias M, Ricard-Andrés MP, Lemes-Castellano A, Abio-Calvete M, Cedena-Romero MT, González-Fernández FA, Llorente-González L, Periago-Peralta AM, de-la-Iglesia-Íñigo S, Méndez M, Morán-Jiménez MJ
Eur J Haematol 2018 Sep;101(3):368-378. Epub 2018 Jul 27 doi: 10.1111/ejh.13112. PMID: 29901818
Denecke J, Marquardt T
Biochim Biophys Acta 2009 Sep;1792(9):915-20. Epub 2008 Dec 25 doi: 10.1016/j.bbadis.2008.12.005. PMID: 19150496
Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, Griesshammer A, Marquardt T, Janka-Schaub G, Kron M, Kohne E
Blood 2003 Dec 15;102(13):4576-81. Epub 2003 Aug 21 doi: 10.1182/blood-2003-02-0613. PMID: 12933587
Marks PW, Mitus AJ
Am J Hematol 1996 Jan;51(1):55-63. doi: 10.1002/(SICI)1096-8652(199601)51:1<55::AID-AJH9>3.0.CO;2-6. PMID: 8571938

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