DeCure for Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAnemia, congenital dyserythropoietic, type IIIb, autosomal recessive maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for anemia, congenital dyserythropoietic, type iiib, autosomal recessive is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
Rac GTPase activating protein 1 (RACGAP1) — RACGAP1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet af3drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5C2K · 1.42 Å · ligand ALUMINUM FLUORIDE (AF3). Experimental structure, not a prediction.
What the evidence adds up to
The 2009 study of 42 patients with congenital dyserythropoietic anaemia type II found 22 mutations in the SEC23B gene, including seven novel ones. Patients with one missense and one nonsense mutation tended to have more severe clinical presentation, lower reticulocyte count, higher serum ferritin, and in some cases more pronounced transfusion needs than patients with two missense mutations. No patient was homozygous or compound heterozygous for two nonsense mutations, suggesting that genotype is never completely null. The overlap between the two categories was noted, meaning genotype alone does not reliably predict severity.
The 1972 report described three children from one family with CDA type II who had Gaucher-like histiocytes in bone marrow, a feature not previously reported in this disease. Endogenous carbon monoxide production and erythrocyte chromium-51 survival indicated significant erythrocyte haemolysis originating in the marrow. A recessive mode of inheritance was suggested, with heterozygotes showing only serological abnormalities.
Several case reports describe very rare CDA variants. The 2017 report identified the fifth case of CDA type IV. The 2020 report added a ninth case of CDA type IV with a novel KLF1 gene mutation. The 1996 report described four patients with marked macrocytosis, little or no anaemia, and vitamin B12- and folate-independent megaloblastic erythropoiesis, without features diagnostic of CDA types I or III; two of these patients were siblings, suggesting autosomal recessive inheritance. The 1985 report described a family with mild anaemia, marked dyserythropoiesis, prominent ringed sideroblasts, microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, and bone marrow erythroid hyperplasia; the authors proposed the designation 'variant congenital dyserythropoietic anaemia with ringed sideroblasts' and noted autosomal recessive inheritance.
What is still missing is any controlled trial of a drug for any subtype of congenital dyserythropoietic anaemia. The literature consists entirely of genetic characterisation and case descriptions. No therapy has been tested in a prospective, randomised fashion. Patient numbers are extremely small, and no stratification by genotype or severity has been used to guide a treatment study. Funding for such trials is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2009 · 62 citations · open access
Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship
AbstractBACKGROUND: The most frequent form of congenital dyserythropoietic anemia is the type II form. Recently it was shown that the vast majority of patients with congenital dyserythropoietic anemia type II carry mutations in the SEC23B gene. Here we established the molecular basis of 42 cases of congenital dyserythropoietic anemia type II and attempted to define a genotype-phenotype relationship. DESIGN AND METHODS: SEC23B gene sequencing analysis was performed to assess the diversity and incidence of each mutation in 42 patients with congenital dyserythropoietic anemia type II (25 described exclusively in this work), from the Italian and the French Registries, and the relationship of these mutations with the clinical presentation. To this purpose, we divided the patients into two groups: (i) patients with two missense mutations and (ii) patients with one nonsense and one missense mutation. RESULTS: We found 22 mutations of uneven frequency, including seven novel mutations. Compound heterozygosity for a missense and a nonsense mutation tended to produce a more severe clinical presentation, a lower reticulocyte count, a higher serum ferritin level, and, in some cases, more pronounced transfusion needs, than homozygosity or compound heterozygosity for two missense mutations. Homozygosity or compound heterozygosity for two nonsense mutations was never found. CONCLUSIONS: This study allowed us to determine the most frequent mutations in patients with congenital dyserythropoietic anemia type II. Correlations between the mutations and various biological parameters suggested that the association of one missense mutation and one nonsense mutation was significantly more deleterious that the association of two missense mutations. However, there was an overlap between the two categories.
Clinical Case Reports · 2017 · 30 citations · open access
A case of congenital dyserythropoietic anemia type IV
AbstractCongenital dyserythropoietic anemias (CDAs) are displayed by ineffective erythropoiesis. The wide variety of phenotypes observed in CDA patients makes differential diagnosis difficult; identification of the genetic variants is crucial in clinical management. We report the fifth case of a patient with unclassified CDAs, after genetic study, with CDA type IV.
AbstractThree children from a family with 10 members had congenital dyserythropoietic anemia, type II. These cases differ from those previously described in that Gaucher-like histiocytes were present in bone marrow aspirates from all affected children. The light and electron microscopic appearance of these cells resembled those described in chronic myelogenous leukemia and thalassemia. Using the endogenous carbon monoxide production as an index of total heme turnover and the erythrocyte 51Cr survival as an index of peripheral destruction, significant erythrocyte hemolysis was shown in the marrow. A recessive mode of inheritance is suggested, with the homozygous person having clinical disease and the heterozygous person having only serological abnormalities.
Journal of Pediatric Hematology/Oncology · 2020 · 15 citations
A Very Rare Congenital Dyserythropoietic Anemia Variant—Type IV in a Patient With a Novel Mutation in the KLF1 Gene: A Case Report and Review of the Literature
AbstractCongenital dyserythropoietic anemias comprise a group of very rare hereditary disorders characterized by ineffective erythropoiesis and distinct morphologic abnormalities of the erythroblasts in the bone marrow. The wide variety of phenotypes observed in these patients makes the diagnosis difficult; identification of the genetic variants is crucial in differential diagnosis and clinical management. We report the nineth case with congenital dyserythropoietic anemia type IV, with a novel mutation that has not been reported before.
British Journal of Haematology · 1996 · 13 citations
Congenital dyserythropoiesis characterized by marked macrocytosis, vitamin B<sub>12</sub>‐ and folate‐independent megaloblastic change and absence of the defining features of congenital dyserythropoietic anaemia types I or III
AbstractFour patients with congenital dyserythropoiesis characterized by marked macrocytosis, little or no anaemia, and vitamin B12- and folate-independent megaloblastic erythropoiesis are reported. Their erythroblasts also showed various dysplastic changes but not those diagnostic for congenital dyserythropoietic anaemia (CDA) types I or III. The haematological features of the four patients, who included two siblings, resemble those of a previously reported patient and together these patients form a recognizable subgroup within those cases of CDA not belonging to CDA types I-III. In two of the cases studied, and possibly a third, the inheritance was as an autosomal recessive character.
Variant congenital dyserythropoietic anaemia with ringed sideroblasts
AbstractA family is described with mild anaemia characterized by marked dyserythropoiesis and by prominent ringed sideroblasts. Inheritance is autosomal recessive. Other features include marked microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, bone marrow erythroid hyperplasia and non-specific structural abnormalities of erythroid precursors on electron microscopy. This appears to be a previously unreported type of hereditary anaemia with both dyserythropoiesis and ringed sideroblasts. We propose the designation 'variant congenital dyserythropoietic anaemia with ringed sideroblasts'.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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