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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 a rare group of inherited blood disorders that affects the development of red blood cells. In people with CDA, immature red blood cells do not develop into normal, mature cells. As a result, affected individuals have a significant reduction in the number of functional red blood cells (anemia). The term "dyserythropoietic" refers to the abnormal red blood cell shape that occurs in people with this condition. People with CDA typically have mild to moderate anemia. In some cases, affected individuals have severe anemia that may require frequent blood transfusions to replenish the supply of red blood cells.

The signs and symptoms of CDA can include tiredness (fatigue), weakness, yellowing of the skin and eyes (jaundice), and an enlarged liver and spleen (hepatosplenomegaly). CDA also causes the body to absorb too much iron (iron overload), which can damage tissues and organs.

There are multiple types of CDA. Each type has a different genetic cause and distinct but overlapping patterns of signs and symptoms.

CDA type I is characterized by moderate to severe anemia that typically begins in childhood or adolescence, although the condition can be detected before birth in some cases. In addition to the signs and symptoms common to all types of CDA, individuals with CDA type I can have skeletal issues, including short stature or abnormalities of the fingers or toes.

The anemia associated with CDA type II can range from mild to severe, and it usually develops in adolescence or early adulthood. Individuals with CDA type II may develop hard deposits in the gallbladder called gallstones in addition to the usual signs and symptoms of CDA.

CDA type III can result in anemia that ranges from mild to severe, depending on the genetic cause, and typically begins in infancy or childhood. Some people with CDA type III do not receive a diagnosis until later in life because they have very mild symptoms. In some cases, individuals with CDA type III develop a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). Some people with CDA type III have eye abnormalities that can cause vision impairment.

CDA type IV is characterized by moderate to severe anemia that typically develops early in life, although the condition can be detected before birth in some cases. Affected individuals can have extensive swelling caused by fluid accumulation before birth (hydrops fetalis). In addition to the signs and symptoms that are common to all types of CDA, individuals with CDA type IV often have short stature. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Russo R, Andolfo I, Manna F, Gambale A, Marra R, Rosato BE, Caforio P, Pinto V, Pignataro P, Radhakrishnan K, Unal S, Tomaiuolo G, Forni GL, Iolascon A
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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
Renella R, Wood WG
Hematol Oncol Clin North Am 2009 Apr;23(2):283-306. doi: 10.1016/j.hoc.2009.01.010. PMID: 19327584
Wickramasinghe SN
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Diagnosis

Iolascon A, Andolfo I, Russo R
Blood 2020 Sep 10;136(11):1274-1283. doi: 10.1182/blood.2019000948. PMID: 32702750
Stern SM, Ferguson PJ
Rheum Dis Clin North Am 2013 Nov;39(4):735-49. Epub 2013 Aug 17 doi: 10.1016/j.rdc.2013.05.002. PMID: 24182852Free PMC Article
Renella R, Wood WG
Hematol Oncol Clin North Am 2009 Apr;23(2):283-306. doi: 10.1016/j.hoc.2009.01.010. PMID: 19327584
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
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Hematol J 2004;5 Suppl 3:S191-4. doi: 10.1038/sj.thj.6200451. PMID: 15190307

Therapy

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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Iancu TC
Mol Aspects Med 1983;6(1):1-100. doi: 10.1016/0098-2997(83)90004-3. PMID: 6371428

Prognosis

Uygun V, Russo R, Karasu G, Daloğlu H, Iolascon A, Yeşilipek A
J Pediatr Hematol Oncol 2020 Aug;42(6):e507-e510. doi: 10.1097/MPH.0000000000001612. PMID: 31593005
Iolascon A, Russo R, Delaunay J
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Wickramasinghe SN
Curr Opin Hematol 2000 Mar;7(2):71-8. doi: 10.1097/00062752-200003000-00001. PMID: 10698292

Clinical prediction guides

Acierno S, Angrisani F, Marino A, Caporali RF, Cimaz R, Giani T
Int J Rheum Dis 2022 Nov;25(11):1333-1338. Epub 2022 Aug 24 doi: 10.1111/1756-185X.14425. PMID: 36004431
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
Avidan N, Tamary H, Dgany O, Cattan D, Pariente A, Thulliez M, Borot N, Moati L, Barthelme A, Shalmon L, Krasnov T, Ben-Asher E, Olender T, Khen M, Yaniv I, Zaizov R, Shalev H, Delaunay J, Fellous M, Lancet D, Beckmann JS
Eur J Hum Genet 2003 Jul;11(7):497-502. doi: 10.1038/sj.ejhg.5200991. PMID: 12825070
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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