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Congenital dyserythropoietic anemia, type III(CDAN3A)

MedGen UID:: 1801596
•Concept ID:: C5676874
•: Disease or Syndrome

Synonyms:	ANEMIA WITH MULTINUCLEATED ERYTHROBLASTS; CDAN3A; Dyserythropoietic anemia, congenital type 3; ERYTHRORETICULOSIS, HEREDITARY BENIGN
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. Autosomal recessive inheritance (Orphanet) Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	KIF23 (15q23)

Monarch Initiative:	MONDO:0007109
OMIM®:	105600
Orphanet:	ORPHA98870

Definition

Congenital dyserythropoietic anemia type IIIa (CDAN3A) is a rare autosomal dominant hematologic disorder characterized by nonprogressive mild to moderate hemolytic anemia, macrocytosis in the peripheral blood, intravascular hemolysis, and giant multinucleated erythroblasts in the bone marrow. The disorder results from ineffective erythropoiesis. Laboratory studies show evidence of intravascular hemolysis, including increased thymidine kinase, lactate dehydrogenase, and/or undetectable haptoglobin (summary by Lind et al., 1995; Liljeholm et al., 2013). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see 224120. [from OMIM]

Clinical features

From HPO

Hemosiderinuria

MedGen UID:: 775752
•Concept ID:: C2721579
•: Disease or Syndrome

The presence of hemosiderin in the urine.

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Jaundice

MedGen UID:: 43987
•Concept ID:: C0022346
•: Sign or Symptom

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

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Macrocytic anemia

MedGen UID:: 1920
•Concept ID:: C0002886
•: Disease or Syndrome

A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).

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Anemia of inadequate production

MedGen UID:: 95937
•Concept ID:: C0392708
•: Pathologic Function

A kind of anemia characterized by inadequate production of erythrocytes.

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Diamond-Blackfan anemia

MedGen UID:: 266045
•Concept ID:: C1260899
•: Disease or Syndrome

Diamond-Blackfan anemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50%, and growth deficiency in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia or no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma.

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Increased circulating lactate dehydrogenase concentration

MedGen UID:: 1377250
•Concept ID:: C4477095
•: Finding

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

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Reduced haptoglobin level

MedGen UID:: 1686017
•Concept ID:: C5209264
•: Finding

An abnormally low concentration of haptoglobin in the blood circulation. Decreased haptoglobin in conjunction with increased reticulocyte count and anemia may indicate hemolysis. Decreased haptoglobin levels can also occur in the absence of hemolysis, due to cirrhosis of the liver, disseminated ovarian carcinomatosis, pulmonary sarcoidosis, and elevated estrogen state.

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Abnormality of blood and blood-forming tissues
Abnormality of metabolism/homeostasis
- Increased circulating lactate dehydrogenase concentration
- Reduced haptoglobin level
Abnormality of the digestive system
- Jaundice
Abnormality of the genitourinary system
- Hemosiderinuria

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Phenotypic abnormality
- Abnormality of blood and blood-forming tissues
  - Abnormal erythrocyte morphology
    - Anemia
      - Congenital anemia
        Congenital dyserythropoietic anemia
        Congenital dyserythropoietic anemia, type III

Professional guidelines

PubMed

Ineffective erythropoiesis and its treatment.

Cazzola M
Blood 2022 Apr 21;139(16):2460-2470. doi: 10.1182/blood.2021011045. PMID: 34932791

The pathogenesis, diagnosis and management of congenital dyserythropoietic anaemia type I.

Roy NBA, Babbs C
Br J Haematol 2019 May;185(3):436-449. Epub 2019 Mar 5 doi: 10.1111/bjh.15817. PMID: 30836435 Free PMC Article

Diagnosis and management of congenital dyserythropoietic anemias.

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

See all (19)

Recent clinical studies

Etiology

Distal limb anomalies in patients with congenital dyserythropoietic anemia.

Amir AZ, Horev G, Yacobovich J, Bennett M, Tamary H
Am J Med Genet A 2017 Feb;173(2):487-490. Epub 2016 Oct 19 doi: 10.1002/ajmg.a.38012. PMID: 27759939

Congenital dyserythropoietic anemia type III.

Sandström H, Wahlin A
Haematologica 2000 Jul;85(7):753-7. PMID: 10897128

See all (2)

Diagnosis

Distal limb anomalies in patients with congenital dyserythropoietic anemia.

Amir AZ, Horev G, Yacobovich J, Bennett M, Tamary H
Am J Med Genet A 2017 Feb;173(2):487-490. Epub 2016 Oct 19 doi: 10.1002/ajmg.a.38012. PMID: 27759939

Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23.

Liljeholm M, Irvine AF, Vikberg AL, Norberg A, Month S, Sandström H, Wahlin A, Mishima M, Golovleva I
Blood 2013 Jun 6;121(23):4791-9. Epub 2013 Apr 9 doi: 10.1182/blood-2012-10-461392. PMID: 23570799

New sporadic case of congenital dyserythropoietic anemia type III in an aged woman: detailed description of ultrastructural findings.

Sigler E, Shaft D, Shtalrid M, Shvidel L, Berrebi A, Resnitzky P
Am J Hematol 2002 May;70(1):72-6. doi: 10.1002/ajh.10086. PMID: 11994986

Congenital dyserythropoietic anemia type III associated with congenital atrioseptal defect has led to severe cardiac problems in a 32-year-old patient.

Röhrig G, Kilter H, Beuckelmann D, Kröner A, Scheid C, Diehl V, Söhngen D
Am J Hematol 2000 Aug;64(4):314-6. doi: 10.1002/1096-8652(200008)64:4<314::aid-ajh14>3.0.co;2-o. PMID: 10911387

Congenital dyserythropoietic anemia type III.

Sandström H, Wahlin A
Haematologica 2000 Jul;85(7):753-7. PMID: 10897128

See all (6)

Prognosis

Differential tissue specific expression of Kif23 alternative transcripts in mice with the human mutation causing congenital dyserythropoietic anemia type III.

Vikberg AL, Malla S, Golovleva I
Blood Cells Mol Dis 2020 Nov;85:102483. Epub 2020 Jul 31 doi: 10.1016/j.bcmd.2020.102483. PMID: 32818800

Distal limb anomalies in patients with congenital dyserythropoietic anemia.

Amir AZ, Horev G, Yacobovich J, Bennett M, Tamary H
Am J Med Genet A 2017 Feb;173(2):487-490. Epub 2016 Oct 19 doi: 10.1002/ajmg.a.38012. PMID: 27759939

Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23.

New sporadic case of congenital dyserythropoietic anemia type III in an aged woman: detailed description of ultrastructural findings.

Sigler E, Shaft D, Shtalrid M, Shvidel L, Berrebi A, Resnitzky P
Am J Hematol 2002 May;70(1):72-6. doi: 10.1002/ajh.10086. PMID: 11994986

Long-term cinemicrography of erythroblasts from a patient with congenital dyserythropoietic anemia type III: direct observation of dysplastic erythroblast formation.

Furukawa T, Inoue H, Sugita K, Eguchi M, Sakakibara H, Sugiyama S, Suda T
Blood Cells 1993;19(2):493-506; discussion 507-8. PMID: 8312576

See all (5)