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Congenital Dyserythropoietic Anemia

Congenital Dyserythropoietic Anemia (CDA) — Comprehensive Disease Characteristics Report

2026-06-05
Falcon MONDO:0019403 Model: Edison Scientific Literature 29 citations

Congenital Dyserythropoietic Anemia (CDA) — Comprehensive Disease Characteristics Report

Target disease

  • Disease name: Congenital dyserythropoietic anemia (CDA)
  • Category: Mendelian / inherited anemia
  • MONDO ID: MONDO_0019403 (OpenTargets) (OpenTargets Search: congenital dyserythropoietic anemia)

1. Disease information

1.1 Concise overview / definition

Congenital dyserythropoietic anemias are inherited disorders of erythropoiesis characterized by ineffective erythropoiesis with distinctive morphologic abnormalities of erythroid precursors and variable hemolysis and iron overload. A recent CDA type II mini-review states: “Congenital dyserythropoietic anemia (CDA) is characterized by anemia—mild to severe, hemolysis, ineffective erythropoiesis, and in some cases, iron overload.” (published 2024-07-05) (akpan2024congenitaldyserythropoieticanemia pages 1-2). A Blood review further frames CDAs as “a heterogeneous group of inherited anemias” affecting erythroid differentiation–proliferation and classified by morphology/clinical/genetic features (published 2020-07, URL below) (iolascon2020congenitaldyserythropoieticanemias. pages 1-1).

1.2 Key identifiers (with availability notes)

1.3 Common synonyms / alternative names

  • “Congenital dyserythropoietic anemias (CDAs)” (plural group term) (iolascon2020congenitaldyserythropoieticanemias. pages 1-1)
  • “CDA type I/II/III/IV”; “transcription factor–related CDA”; “X-linked thrombocytopenia with dyserythropoietic anemia (XLTDA)” (saptarshi2023developmentofhighresolution pages 1-2, musri2023newcasesand pages 1-2, iolascon2020congenitaldyserythropoieticanemias. pages 1-1)

1.4 Evidence provenance (patient-level vs aggregated)

The information summarized here derives from both: - Aggregated disease-level reviews and mechanistic synthesis (e.g., Blood review; Curr Opin Hematol review) (iolascon2020congenitaldyserythropoieticanemias. pages 1-1, king2022thecongenitaldyserythropoieitic pages 1-3) - Patient-series / molecular cohorts (e.g., 9-case SEC23B cohort; 11-case Indian diagnostic cohort) (musri2023newcasesand pages 1-2, saptarshi2023developmentofhighresolution pages 1-2) - Registries (real-world evidence infrastructure): North American CDA registry (CDAR) and French national registry initiative (ClinicalTrials.gov) (NCT02964494 chunk 1, NCT03983629 chunk 1)

Key recent sources prioritized (2023–2024): Akpan 2024 (Frontiers in Hematology), Musri 2023 (IJMS), Saptarshi 2023 (Italian J Pediatrics) (akpan2024congenitaldyserythropoieticanemia pages 1-2, musri2023newcasesand pages 1-2, saptarshi2023developmentofhighresolution pages 1-2).

2. Etiology

2.1 Primary causes

CDA is genetic (Mendelian) and caused by pathogenic variants in genes required for erythroblast maturation, vesicular trafficking/glycosylation, cytokinesis, or transcriptional control of erythropoiesis.

Examples in retrieved evidence: - CDA I: mutations in CDAN1 and CDIN1 (previously C15orf41) (scott2020recapitulationoferythropoiesis pages 1-2, king2022thecongenitaldyserythropoieitic pages 1-3) - CDA II: biallelic pathogenic variants in SEC23B (akpan2024congenitaldyserythropoieticanemia pages 1-2, musri2023newcasesand pages 1-2) - Additional/rare CDA genes are noted in disease–target association resources (OpenTargets) including KIF23, RACGAP1, GATA1, KLF1, LPIN2 (OpenTargets Search: congenital dyserythropoietic anemia).

2.2 Risk factors

2.3 Protective factors

No specific genetic or environmental protective factors were identified in the retrieved sources.

2.4 Gene–environment interactions

No specific CDA gene–environment interaction studies were identified in the retrieved sources.

3. Phenotypes

3.1 Shared clinical/laboratory phenotype across CDAs

Across CDA subtypes, a consistent pattern is chronic anemia with hemolysis markers and suboptimal reticulocytosis for the severity of anemia (ineffective erythropoiesis). A review notes that CDA is characterized by elevated LDH/indirect bilirubin (hemolysis) while the reticulocyte count is “normal or suboptimally elevated” because of ineffective erythropoiesis (king2022thecongenitaldyserythropoieitic pages 1-3). The French registry summary similarly describes anemia that is “non-regenerative or inappropriate regarding anaemia” with “moderate unconjugated hyperbilirubinemia” and frequent splenomegaly/jaundice (NCT03983629 chunk 1).

Common complications: gallstones, splenomegaly/hypersplenism, and iron overload/hemochromatosis even without transfusions (akpan2024congenitaldyserythropoieticanemia pages 1-2, musri2023newcasesand pages 1-2, king2022thecongenitaldyserythropoieitic pages 1-3, NCT03983629 chunk 1).

3.2 CDA II phenotype (examples of 2023–2024 data)

  • Akpan 2024 describes CDA II as autosomal recessive hemolytic disease due to SEC23B variants, and notes peripheral smear anisopoikilocytosis with basophilic stippling and rare binucleated mature erythroblasts, and hemolytic anemia with inadequate reticulocytosis (akpan2024congenitaldyserythropoieticanemia pages 1-2).
  • Musri 2023 additionally lists complications such as “leg ulcers,” “aplastic crisis,” and “bulky extramedullary erythropoiesis,” and notes marrow with >10% bi/multinucleated erythroblasts, and an EM feature of an “additional membrane consisting of residual endoplasmic reticulum beneath the cytoplasmic membrane” (musri2023newcasesand pages 1-2).
  • A severe adult case report (2024) illustrates the clinical range (Hb 3.7 g/dL; ferritin 1,880 ng/mL; transferrin saturation 96.08%) and emphasizes negative Coombs and the role of gene panels in delayed diagnosis (shemawat2024congenitaldyserythropoieticanemia pages 1-2).

3.3 CDA I phenotype (examples)

CDA I is described as an autosomal recessive disease with macrocytic anemia and a pathognomonic “spongy heterochromatin” in erythroblasts (noylotan2021cdan1isessential pages 1-2). In cultured patient erythroid cells, a Haematologica study states CDA-I is caused by mutations in CDAN1 and CDIN1, and reports defects including delayed terminal erythroid differentiation and nucleolar abnormalities (scott2020recapitulationoferythropoiesis pages 1-2).

3.4 Phenotype characteristics (onset, progression, severity)

3.5 Quality-of-life impact

No disease-specific QoL instrument results (e.g., SF-36, PROMIS, EQ-5D) were identified in the retrieved sources. Clinically, persistent anemia, transfusion dependence, iron overload management, and complications (splenomegaly, gallstones, extramedullary hematopoiesis) plausibly impair daily functioning; however, quantitative QoL data should be added from dedicated QoL studies not captured in this retrieval.

3.6 Suggested HPO terms (non-exhaustive)

(Ontology suggestions for knowledge base mapping; not all are explicitly labeled as HPO in the retrieved sources.) - HP:0001903 Anemia - HP:0001878 Hemolytic anemia - HP:0002188 Elevated indirect bilirubin / unconjugated hyperbilirubinemia - HP:0000980 Jaundice - HP:0001744 Splenomegaly - HP:0003270 Iron overload / hemochromatosis - HP:0003155 Elevated serum ferritin - HP:0002240 Hepatomegaly - HP:0001082 Abnormality of bone marrow morphology (dyserythropoiesis) - HP:0004396 Cholelithiasis / gallstones - HP:0001764 Aplastic crisis (CDA II complication reported) (musri2023newcasesand pages 1-2)

4. Genetic / molecular information

4.1 Causal genes and inheritance (core)

4.2 Pathogenic variants (examples with HGVS nomenclature; 2023 priority)

SEC23B variants in a 9-case cohort (Musri 2023; published 2023-06-09): - The abstract states: “we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel.” (musri2023newcasesand pages 1-2). - Novel variants reported include: p.Thr445Arg, p.Tyr579Cys, p.Arg701His, p.Asp693GlyfsTer2, c.1512-2A>G, and complex intronic c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT (musri2023newcasesand pages 1-2).

Indian recurrent variant and diagnostic screening (Saptarshi 2023; published 2023-07-07): - Abstract reports: “The most common mutation reported in India is c.1385 A>G, p.Y462C.” and describes 11 patients with homozygous p.Y462C, with heterozygous parents (saptarshi2023developmentofhighresolution pages 1-2).

4.3 Variant classes and functional consequences (SEC23B examples)

Musri 2023 reports computational and patient-derived cell evidence consistent with loss-of-function/protein deficiency: “Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation.” (musri2023newcasesand pages 1-2). RT-PCR/Sanger data showed aberrant splicing for complex intronic alleles (exon 13–14 skipping) (musri2023newcasesand pages 1-2).

4.4 Modifier genes / variants (iron overload severity)

A Blood review summarizes modifier concepts for iron overload in CDA II, including genetic modifiers such as HFE variants and an erythroferrone (ERFE) coding variant (p.A260S) associated with altered iron regulation (iolascon2020congenitaldyserythropoieticanemias. pages 12-13).

4.5 Epigenetic information

No CDA-specific epigenetic (methylation/histone modification) findings were identified in the retrieved sources.

4.6 Chromosomal abnormalities

No recurrent chromosomal abnormalities were identified in the retrieved sources.

5. Environmental information

CDA is primarily genetic. No specific environmental toxins, lifestyle factors, or infectious triggers were identified as causal in the retrieved sources.

6. Mechanism / pathophysiology

6.1 Unifying mechanism: ineffective erythropoiesis → anemia ± hemolysis

Akpan 2024 defines ineffective erythropoiesis as inadequate reticulocytosis in the presence of immature precursors, with an “erythropoietin-driven expansion of erythroid precursors and apoptosis of late-stage erythroid precursors” (akpan2024congenitaldyserythropoieticanemia pages 1-2). This links upstream erythroid maturation failure to downstream anemia/hemolysis phenotypes.

Suggested GO biological process terms (examples): - erythrocyte differentiation; erythrocyte maturation; regulation of erythropoiesis; apoptotic process

Suggested CL cell types: - erythroblast; late erythroid precursor; reticulocyte

6.2 Iron overload: ERFE–hepcidin axis (central downstream pathway)

Akpan 2024 states that ineffective erythropoiesis causes “overexpression of erythroferrone” that “suppresses hepcidin leading to increased iron absorption and progressive iron overload” (akpan2024congenitaldyserythropoieticanemia pages 1-2). The Blood review similarly highlights erythroferrone as an erythroblast-derived inhibitor of hepcidin in CDA II (iolascon2020congenitaldyserythropoieticanemias. pages 1-1).

Causal chain (simplified): Genetic subtype defect → ineffective erythropoiesis → ↑EPO drive/precursor expansion and apoptosis → ↑erythroferrone (ERFE) → ↓hepcidin → ↑intestinal iron absorption → hepatic/systemic iron overload (akpan2024congenitaldyserythropoieticanemia pages 1-2, iolascon2020congenitaldyserythropoieticanemias. pages 1-1).

6.3 CDA II mechanism: SEC23B / COPII trafficking and hypoglycosylation

Suggested GO cellular component terms (examples): - endoplasmic reticulum; Golgi apparatus; COPII-coated vesicle

6.4 CDA I mechanism: CDAN1/CDIN1 and erythroid nuclear/chromatin pathology

A CDA-I model paper states CDA I is “mainly caused by mutations in CDAN1” and demonstrates erythroid-lineage deletion causes severe embryonic anemia with the pathognomonic “spongy heterochromatin” and increased apoptotic erythroblasts (noylotan2021cdan1isessential pages 1-2). In human CDA-I erythroid culture, cells show delayed terminal differentiation and chromatin accessibility changes, with CDAN1/CDIN1 enrichment in abnormal nucleoli (scott2020recapitulationoferythropoiesis pages 1-2).

7. Anatomical structures affected

7.1 Organ-level

Suggested UBERON terms (examples): bone marrow; spleen; liver; gallbladder

7.2 Tissue/cell level

7.3 Subcellular level

8. Temporal development

8.1 Onset

Diagnosis is commonly made in childhood, but can be delayed for years; French registry summary explicitly notes heterogeneity can delay diagnosis (NCT03983629 chunk 1). A 30-year-old adult CDA II case demonstrates late diagnosis in practice (shemawat2024congenitaldyserythropoieticanemia pages 1-2).

8.2 Progression and course

Chronic course with variable anemia severity; progressive iron loading can occur even without transfusions due to increased absorption (NCT03983629 chunk 1, akpan2024congenitaldyserythropoieticanemia pages 1-2).

9. Inheritance and population

9.1 Epidemiology (statistics)

  • A 2022 review provides estimated prevalence: CDA II ~0.71 cases/million and CDA I ~0.24 cases/million, with underdiagnosis suspected; it also cites a more recent estimate of CDA I incidence of 5 cases/million live births (king2022thecongenitaldyserythropoieitic pages 1-3).
  • The French registry protocol summary reports international variation: “varies between countries from 0.08 million in Scandinavia to 2.6 cases/million inhabitants in Italy” (NCT03983629 chunk 1).

9.2 Inheritance patterns

9.3 Population distribution / founder effects

10. Diagnostics

10.1 Core clinical tests and morphology

A 2024 mini-review states evaluation “includes basic laboratory testing… MRI… bone marrow assessment, and genetic testing” (akpan2024congenitaldyserythropoieticanemia pages 1-2). It also specifies labs useful for ineffective erythropoiesis evaluation (indirect bilirubin, reticulocyte production index <2, and iron panel) (akpan2024congenitaldyserythropoieticanemia pages 1-2).

Key morphologic criteria (examples): - CDA II marrow: “more than 10% of mature bi- or multi-nucleated erythroblasts” (musri2023newcasesand pages 1-2).

10.2 Specialized assays for CDA II vs membrane disorders

Saptarshi 2023 explains that CDA II has band 3 hypoglycosylation and can show decreased mean channel fluorescence on EMA testing (a pitfall with hereditary spherocytosis), and uses anti-CD44 antibody binding plus molecular confirmation (saptarshi2023developmentofhighresolution pages 1-2).

10.3 Genetic testing strategy and real-world implementations

10.4 Differential diagnosis

Registries and reviews note overlap with hereditary hemolytic anemias and acquired dyserythropoiesis, complicating diagnosis (NCT02964494 chunk 1, akpan2024congenitaldyserythropoieticanemia pages 1-2).

11. Outcome / prognosis

Robust survival and cause-specific mortality statistics were not identified in the retrieved sources. Registry protocols explicitly highlight these as unanswered questions (median survival, causes of death) and motivate long-term follow-up registries (NCT03983629 chunk 1). Prognosis is therefore best represented as variable, driven by anemia severity and iron overload burden, with registries designed to quantify long-term outcomes (NCT02964494 chunk 1, NCT03983629 chunk 1).

12. Treatment

12.1 Supportive care and escalation (real-world standard practice)

A 2024 mini-review states management is phenotype-dependent and “some severe cases may require blood transfusion, iron chelation therapy, splenectomy, and in extreme cases, hematopoietic stem cell transplant may be necessary.” (akpan2024congenitaldyserythropoieticanemia pages 1-2). The Blood review describes routine monitoring and includes transfusion support for severe anemia and HSCT in severe cases (iolascon2020congenitaldyserythropoieticanemias. pages 12-13).

12.2 Interferon-α for CDA I

A CDA I model paper notes: “for some patients, administration of interferon-α (INF-α) improves anemia and normalizes erythroid morphology… although this treatment has significant toxicities.” (noylotan2021cdan1isessential pages 1-2). Registry endpoints also track interferon efficacy (NCT03983629 chunk 1).

12.3 Iron overload management

Given ERFE–hepcidin-driven absorption and transfusional exposure, iron monitoring and treatment are core (akpan2024congenitaldyserythropoieticanemia pages 1-2, NCT03983629 chunk 1). Akpan 2024 provides a management monitoring summary table (Table 1) (akpan2024congenitaldyserythropoieticanemia media 60f6d3ed).

12.4 Curative therapy: hematopoietic stem cell transplantation (HSCT)

HSCT is described as a curative option for severe CDA cases in review-level evidence (iolascon2020congenitaldyserythropoieticanemias. pages 12-13, akpan2024congenitaldyserythropoieticanemia pages 1-2).

12.5 Suggested MAXO terms (examples)

  • Red blood cell transfusion
  • Iron chelation therapy
  • Splenectomy
  • Hematopoietic stem cell transplantation
  • Genetic counseling

12.6 Clinical trials / registries (current applications)

  • NCT02964494 (CDAR): North American CDA registry; recruiting; started 2016-08-29, updated 2025-05-15; collects long-term natural history, complications, and treatment effects (NCT02964494 chunk 1).
  • URL: https://clinicaltrials.gov/study/NCT02964494 (NCT02964494 chunk 1)
  • NCT03983629: French national registry; first posted 2019-06-12; includes WES/WGS and tracks interferon efficacy and survival-related outcomes (NCT03983629 chunk 1).
  • URL: https://clinicaltrials.gov/study/NCT03983629 (NCT03983629 chunk 1)

13. Prevention

Primary prevention is not generally feasible because CDA is genetic; however, secondary/tertiary prevention focuses on early diagnosis, transfusion/iron overload management, and family planning. - Prenatal and preimplantation testing become feasible once familial pathogenic variants are identified (noted in CDA literature; and consistent with genetic testing emphasis and registry inclusion of genetic analyses) (NCT03983629 chunk 1, akpan2024congenitaldyserythropoieticanemia pages 1-2).

14. Other species / natural disease

No naturally occurring CDA in non-human species was identified in the retrieved sources.

15. Model organisms

15.1 CDA I models

A 2021 study reports erythroid-specific deletion of Cdan1 causes embryonic lethality from severe anemia and recapitulates ultrastructural “spongy heterochromatin”; it also reports increased apoptosis and impaired maturation marker dynamics (noylotan2021cdan1isessential pages 1-2).

15.2 CDA II models (review evidence)

A 2022 review summarizes that SEC23B overlaps functionally with SEC23A in mice and that erythroid-specific reduction of Sec23 alleles can produce CDAII-like features, with rescue by increasing SEC23A expression (king2022thecongenitaldyserythropoieitic pages 1-3).

Key concepts & expert synthesis (authoritative analysis)

  1. CDA is best approached as a genetic disease group, not a single disorder, with subtype classification anchored in marrow morphology but increasingly confirmed/defined by molecular testing (NGS/WES/WGS) (iolascon2020congenitaldyserythropoieticanemias. pages 1-1, akpan2024congenitaldyserythropoieticanemia pages 1-2, NCT02964494 chunk 1).
  2. Iron overload is not merely transfusional in CDA; it can be mechanistically downstream of ineffective erythropoiesis via ERFE-mediated hepcidin suppression, producing progressive overload even in non-transfused individuals—an important clinical pitfall for monitoring and management (akpan2024congenitaldyserythropoieticanemia pages 1-2, iolascon2020congenitaldyserythropoieticanemias. pages 1-1, NCT03983629 chunk 1).
  3. Real-world implementation is increasingly registry-driven, with multicenter long-term registries explicitly designed to resolve gaps in survival, complications, genotype–phenotype correlations, and treatment effects (NCT02964494 chunk 1, NCT03983629 chunk 1).

Summary table of CDA subtypes

Table (click to expand)
Subtype Key causal gene(s) Inheritance Hallmark bone marrow morphology Key clinical features / complications Key management notes
CDA (group); MONDO: MONDO_0019403 Major associated genes include CDAN1, CDIN1, SEC23B, KIF23, RACGAP1, GATA1, KLF1 (OpenTargets disease–target associations) (OpenTargets Search: congenital dyserythropoietic anemia) Heterogeneous; includes autosomal recessive and X-linked/TF-related forms depending on subtype (OpenTargets Search: congenital dyserythropoietic anemia, iolascon2020congenitaldyserythropoieticanemias. pages 1-1) Bone marrow usually shows erythroid hyperplasia with subtype-specific dyserythropoiesis (iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Inherited anemias with ineffective erythropoiesis; iron overload can occur even without heavy transfusion burden due to erythroferrone-mediated hepcidin suppression; differential diagnosis overlaps with hereditary hemolytic anemias and acquired dyserythropoiesis (iolascon2020congenitaldyserythropoieticanemias. pages 12-13, iolascon2020congenitaldyserythropoieticanemias. pages 1-1, iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Monitoring includes CBC and iron parameters; severe anemia may require transfusion; iron overload should be treated/monitored carefully, especially before HSCT (iolascon2020congenitaldyserythropoieticanemias. pages 12-13, akpan2024congenitaldyserythropoieticanemia media 60f6d3ed)
CDA I CDAN1, CDIN1/C15orf41 (OpenTargets Search: congenital dyserythropoietic anemia) Autosomal recessive (nagar2023congenitaldyserythropoieticanemia pages 10-11) Internuclear chromatin bridges; EM shows “Swiss cheese” / spongy heterochromatin (iolascon2020congenitaldyserythropoieticanemias. pages 24-25, nagar2023congenitaldyserythropoieticanemia pages 10-11) Moderate to severe anemia; hepatosplenomegaly; macrocytosis; hyperbilirubinemia; gallstones; iron overload/hemosiderosis may develop even in non-transfused patients (nagar2023congenitaldyserythropoieticanemia pages 10-11) Mainly supportive care; RBC transfusions as needed; interferon therapy can reduce transfusion dependence; cholecystectomy for symptomatic gallstones; phlebotomy or chelation for iron overload; prenatal/preimplantation testing possible once familial variants are known (iolascon2020congenitaldyserythropoieticanemias. pages 12-13, nagar2023congenitaldyserythropoieticanemia pages 10-11)
CDA II (most common major type) SEC23B (biallelic pathogenic variants) (akpan2024congenitaldyserythropoieticanemia pages 1-2, OpenTargets Search: congenital dyserythropoietic anemia) Autosomal recessive (akpan2024congenitaldyserythropoieticanemia pages 1-2) Binucleate erythroid precursors / erythroblasts with two or more nuclei (iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Mild to severe normocytic anemia, hemolysis, jaundice, splenomegaly, gallstones, liver iron overload; inadequate reticulocytosis despite anemia; ineffective erythropoiesis with ERFE overexpression → hepcidin suppression → increased iron absorption (akpan2024congenitaldyserythropoieticanemia pages 1-2, iolascon2020congenitaldyserythropoieticanemias. pages 12-13) Diagnostic workup: CBC/reticulocytes, bilirubin/haptoglobin, iron studies, MRI for organ iron, bone marrow exam, and genetic testing/NGS; management may include transfusions, iron chelation, splenectomy in selected cases, and HSCT for very severe disease (akpan2024congenitaldyserythropoieticanemia pages 1-2, iolascon2020congenitaldyserythropoieticanemias. pages 12-13, akpan2024congenitaldyserythropoieticanemia media 60f6d3ed)
CDA II: example SEC23B variants Examples reported in recent cohort: c.1334C>G (p.Thr445Arg), c.1736A>G (p.Tyr579Cys), c.2102G>A (p.Arg701His), c.2074_2077dupGATG (p.Asp693GlyfsTer2), c.1512-2A>G, c.1512-3delinsTT with c.1512-16_1512-7delACTCTGGAAT, c.325G>A (p.Glu109Lys), c.40C>T (p.Arg14Trp) (musri2023newcasesand pages 2-4, musri2023newcasesand pages 1-2, musri2023newcasesand pages 4-6, musri2023newcasesand pages 12-13, musri2023newcasesand pages 6-7) Autosomal recessive; variants often occur as homozygous or compound heterozygous alleles (musri2023newcasesand pages 2-4, musri2023newcasesand pages 6-7) Same CDA II morphology; some patients also had abnormal membrane protein electrophoresis / band 3 and EM membrane abnormalities in reported series (musri2023newcasesand pages 4-6) Reported cohorts showed chronic Coombs-negative hemolytic anemia, hepatosplenomegaly, cholelithiasis, iron overload, and transfusion history in some patients (musri2023newcasesand pages 4-6, musri2023newcasesand pages 6-7) Functional studies showed reduced SEC23B protein, limited SEC23A compensation in LCLs, and exon 13–14 skipping for complex intronic alleles; findings support loss-of-function disease mechanism (musri2023newcasesand pages 1-2, musri2023newcasesand pages 9-12, musri2023newcasesand pages 12-13)
CDA III KIF23, RACGAP1 (OpenTargets Search: congenital dyserythropoietic anemia) Not specified in gathered evidence for all forms; genetically distinct subtype (OpenTargets Search: congenital dyserythropoietic anemia, iolascon2020congenitaldyserythropoieticanemias. pages 1-1) Giant multinucleated erythroblasts (iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Rare major subtype within CDA classification; specific phenotype details not fully captured in gathered excerpts (iolascon2020congenitaldyserythropoieticanemias. pages 1-1, iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Supportive care and iron monitoring principles from CDA group apply; subtype-specific evidence in gathered set is limited (iolascon2020congenitaldyserythropoieticanemias. pages 12-13, iolascon2020congenitaldyserythropoieticanemias. pages 24-25)
CDA IV / transcription factor–related and variant forms KLF1, GATA1; broader CDA-associated list in OpenTargets also includes LPIN2 and other rare associations (OpenTargets Search: congenital dyserythropoietic anemia) X-linked or other subtype-specific inheritance may apply for TF-related cytopenias; not fully resolved in gathered excerpts (OpenTargets Search: congenital dyserythropoietic anemia, iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Multinucleate erythroblasts reported for CDA IV; GATA1-related disorders may present as dyserythropoietic anemia with thrombocytopenia rather than classic isolated CDA (iolascon2020congenitaldyserythropoieticanemias. pages 24-25) Includes GATA1-related cytopenias and KLF1-related CDA IV within modern classification; clinical manifestations are heterogeneous and may extend beyond isolated anemia (iolascon2020congenitaldyserythropoieticanemias. pages 1-1, iolascon2020congenitaldyserythropoieticanemias. pages 24-25, OpenTargets Search: congenital dyserythropoietic anemia) No subtype-specific standard therapy detailed in gathered excerpts; diagnosis relies increasingly on molecular testing/NGS and expert hematopathology review (iolascon2020congenitaldyserythropoieticanemias. pages 1-1, iolascon2020congenitaldyserythropoieticanemias. pages 24-25)

Table: This table summarizes major congenital dyserythropoietic anemia subtypes and selected additional/transcription-factor-related forms using only the gathered evidence. It highlights the causal genes, inheritance, hallmark marrow morphology, major clinical features, and practical management points most relevant for a disease knowledge base.

Management monitoring table (image evidence)

Akpan 2024 includes a management/monitoring table (Table 1) summarizing recommended monitoring frequencies across age groups and transfusion status (akpan2024congenitaldyserythropoieticanemia media 60f6d3ed).

Key source URLs and publication dates (from retrieved evidence)

Notable gaps in retrieved evidence (for follow-on curation)

  • ICD-10/ICD-11 and Orphanet identifiers were not captured in the retrieved set.
  • Quantitative QoL outcomes and robust long-term survival statistics were not found; ongoing registries aim to address these (NCT03983629 chunk 1, NCT02964494 chunk 1).

References

  1. (OpenTargets Search: congenital dyserythropoietic anemia): Open Targets Query (congenital dyserythropoietic anemia, 18 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  2. (akpan2024congenitaldyserythropoieticanemia pages 1-2): Imo J. Akpan, Kelsie Bogyo, Rebecca J. Leeman-Neill, Julia Wattacheril, and Richard O. Francis. Congenital dyserythropoietic anemia type ii and ineffective erythropoiesis: challenges in diagnosis and management. Frontiers in Hematology, Jul 2024. URL: https://doi.org/10.3389/frhem.2024.1389820, doi:10.3389/frhem.2024.1389820. This article has 1 citations.

  3. (iolascon2020congenitaldyserythropoieticanemias. pages 1-1): Achille Iolascon, Roberta Russo, and Jean Delaunay. Congenital dyserythropoietic anemias. Blood, 18:146-151, Jul 2020. URL: https://doi.org/10.1182/blood.2019000948, doi:10.1182/blood.2019000948. This article has 128 citations and is from a highest quality peer-reviewed journal.

  4. (NCT03983629 chunk 1): Registry of Congenital Dyserythropoietic Anemia. Lille Catholic University. 2017. ClinicalTrials.gov Identifier: NCT03983629

  5. (saptarshi2023developmentofhighresolution pages 1-2): Arati Nandan Saptarshi, Rashmi K. Dongerdiye, Tejashree Anil More, and Prabhakar S. Kedar. Development of high-resolution melting curve analysis for rapid detection of sec23b gene mutation causing congenital dyserythropoietic anemia type ii in indian population. Italian Journal of Pediatrics, Jul 2023. URL: https://doi.org/10.1186/s13052-023-01493-w, doi:10.1186/s13052-023-01493-w. This article has 4 citations and is from a peer-reviewed journal.

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