DeCure for Anemia, nonspherocytic hemolytic, due to G6PD deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for anemia, nonspherocytic hemolytic, due to G6PD deficiency — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAnemia, nonspherocytic hemolytic, due to G6PD deficiency maps to a 4-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, nonspherocytic hemolytic, due to g6pd deficiency 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
calcium/calmodulin dependent serine protein kinase (CASK) — CASK 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 2r,3s,4r,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3C0I · 1.85 Å · ligand [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate (3AM). Experimental structure, not a prediction.
What the evidence adds up to
A 1969 report describes a Thai boy with congenital nonspherocytic hemolytic anaemia whose G6PD activity was about 5 per cent of normal; the variant, named G6PD Bangkok, was heat-labile and had normal electrophoretic mobility. A 1982 study of a mulatto patient with chronic nonspherocytic hemolytic anaemia found a different variant, G6PD Varadero, with reduced activity, increased thermolability, slightly increased electrophoretic mobility, and a biphasic pH activity profile. In a 2009 case, a 65-year-old Caucasian man with no prior anaemia developed a chronic haemolytic anaemia with a very low erythrocyte G6PD activity (0.6 to 1.5 UI/g Hb, normal 5.3–7.9). Over 16 years his anaemia worsened, requiring 8 to 16 packed red cell transfusions per year. Sequencing revealed a somatic mutation in the G6PD gene in haematopoietic cells only — skin fibroblasts were normal. Of 44 bone marrow CD34+ clones tested, 61 per cent carried the mutation, 7 per cent were unmutated, and the rest showed both genotypes. The authors state this is the first reported case of chronic nonspherocytic anaemia from an acquired somatic G6PD mutation.
A 2004 case-review from Pakistan found that among 3600 adult admissions, 1440 were anaemic and 49 were G6PD deficient, giving a frequency of 3.4 per cent in anaemic patients and 1.36 per cent overall. Antimalarials and sulphonamide antibiotics were the most common triggers of haemolysis. Acute renal failure occurred in five patients, with two deaths. A 2014 case report describes a 2-year-7-month-old boy with a history of neonatal hyperbilirubinemia and severe anaemia requiring transfusion, who presented with haemolytic crisis 48 hours after eating fava beans; G6PD qualitative determination was compatible with deficiency. A 2026 article summarises a case of acute haemolysis after rasburicase infusion and lists other triggering drugs including sulfonamides, nitrofurantoin, antimalarials, dapsone, chloramphenicol, high-dose aspirin, methylene blue, and phenazopyridine.
No treatment or cure is described in any of these abstracts. What remains missing is any prospective trial of a drug to prevent or treat haemolysis in G6PD deficiency, any validated strategy to identify patients at risk of severe complications such as acute renal failure, and any systematic effort to stratify patients by G6PD variant genotype or residual enzyme activity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 1969 · 25 citations · open access
G-6-PD Bangkok: A New Variant Found in Congenital Nonspherocytic Hemolytic Disease (CNHD)
AbstractAbstract A new variant of G-6-PD was found in a Thai boy who had typical clinical and hematologic findings of congenital nonspherocytic hemolytic anemia. This mutant has normal electrophoretic mobility, normal affinity for G-6P and NADP, and is very labile to heat. It has an activity of about 5 per cent of normal and shows increased utilization of 2-deoxyglucose-6-phosphate and NAD and decreased utilization of deamino NADP. It is different from previously described mutants, and is named G-6-PD Bangkok.
Glucose 6 phosphate dehydrogenase deficiency in adults.
AbstractOBJECTIVE: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. DESIGN: Case-review. PLACE AND DURATION OF STUDY: District Headquarter Hospital Batkhela, Malakand Agency, from March 1999 to August 2000. SUBJECTS AND METHODS: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. RESULTS: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. CONCLUSION: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine.
Revista chilena de pediatría · 2014 · 8 citations · open access
Deficiencia de glucosa 6 fosfato deshidrogenasa en niños: Caso clínico
AbstractINTRODUCTION: Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. OBJECTIVE: To analyze the case of a child who presented hemolytic crisis due to favism. CASE REPORT: A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. CONCLUSION: G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.
Journal of the Advanced Practitioner in Oncology · 2026 · 1 citations · open access
A Rare Case of Acute Hemolysis After Rasburicase Infusion
Abstractgene, which provides instructions for manufacturing the G6PD enzyme. G6PD deficiency primarily impacts red blood cells. This deficiency can result in hemolytic anemia (HA), in which rapid destruction of red blood cells occurs due to the vulnerability of erythrocytes to reactive oxygen species. It is most commonly found in males and affects 1 in 10 Black males in the United States. Persons with G6PD deficiency may exhibit symptoms such as pallor, jaundice, dark urine, fatigue, tachycardia, shortness of breath, and splenomegaly. Exposure to certain medications such as rasburicase, sulfonamides, nitrofurantoin, antimalarials, dapsone, chloramphenicol, high-dose aspirin, methylene blue, and phenazopyridine may trigger a hemolytic crisis in those with G6PD deficiency. Tests used in the diagnosis of HA include the Coombs test, haptoglobin, complete blood count, urinalysis, lactate dehydrogenase, bone marrow tests, and a peripheral blood smear. This article summarizes the case of a patient who developed HA after an infusion of rasburicase and offers management strategies.
A Somatic Mutation in the G6PD Gene in Hematopoietic Cells Causes a Chronic Haemolytic Anemia.
AbstractAbstract Abstract 4033 Poster Board III-969 G6PD deficiency is the more common human enzyme defect, leading typically to an acute intravascular hemolysis occurring when red cells are exposed to an oxidative stress. However, in rare patients, very low enzymatic level induces the class I G6PD deficiency according to the WHO classification, i.e. a chronic non-spherocytic hemolytic anemia. These cases are all sporadic, occur worldwide, and almost all arise from de novo independent mutations. These mutations are found at the genomic level in both hematopoietic and non hematopoietic cells and occur recurrently in “hot spots”: most of them are located in the exon 10 of the G6PD gene, implicated in the dimer formation and the stability of the active enzyme. No null or frameshift mutations have been reported yet, probably because such mutations would be lethal; indeed, a minimal residual G6PD activity is essential during embryogenesis. We report here the case of 65 years-old Caucasian man referred in 1993 for hemolytic anemia. No personal or familial history of anemia was noted. Nine and five years before, the hemoglobin (Hb) level and the mean corpuscular volume (MCV) were normal. At diagnosis, the anemia was moderate (Hb: 11.9 g/dL), macrocytic (MCV: 104 fL) and regenerative (reticulocyte count: 550G/L) with hemolytic features. Platelets and leucocytes counts were normal. No clinical or ultrasound spleen enlargement was noted. The screening tests ruled out all the classical causes of acquired hemolytic anemia. Red cells half life after Cr51 labelling was shortened with autologous (5 days) but not with allogenous red cells confirming the corpuscular mechanism of the hemolysis. Dosage of erythocyte G6PD activity revealed a very low level (from 0.6 to 1.5 UI/g of Hb, normal range 5.3-7.9). Pyruvate kinase, pyrimidine 5'-nucleotidase and hexokinase enzymatic activities were increased in agreement with the reticulocytosis. With a follow-up of 16 years, evolution was marked by a progressive worsening of the anemia, requiring 8 to 16 packed red cell transfusions per year in parallel with an iron chelation and folic acid therapy. Concomittantly, the macrocytosis increased up to 144 fL. At the molecular level, sequencing of the genomic DNA of the G6PD gene revealed presence of a single nucleotide mutation that altered the IVS 10 nucleotide 1 G>A from donor consensus sequence, leading to an impaired splicing between exon 10 and exon 11. The missplicing creates a premature termination codon giving theorically a truncated protein (464 versus 514 amino-acid). This severe genotype was discordant with the normal hemoglobin level five years before the diagnosis. Moreover, such a mutation at the germinal level would be expected to be lethal; therefore, we hypothesized that it arised at the somatic level in an hematopoietic stem cell; we measured the G6PD activity in hematopoietic and non hematopoietic cells and observed that it was decreased in red cells, polymorphonuclear cells and lymphocytes from blood, but was normal in skin fibroblasts; molecular analysis confirmed that the mutation was present in blood mononuclear cells but was absent in the fibroblasts. Bone marrow CD34+ cells were then sorted and plated at one cell per dish in the presence of a cocktail of cytokines including EPO and the different clones were harvested at day 10 for genomic analysis of the G6PD gene. Out of the 44 tested clones, we found that most of them carried the mutation (61%), but we were still able to detect a few unmutated clones (7%), reflecting the persistence of a minor polyclonal unmutated hematopoiesis. Surprisingly, we detect in the rest of the clones both the normal and mutated genotypes; at this time, we have no clear explanation to this finding. Acquired modifications of structure or expression of genes implicated in red cell physiology have been long recognized, occurring principally in myeloid malignancies such as myelodysplastic syndromes (MDS). This includes genes implicated in the red cell membrane skeleton or in haemoglobin synthesis or structure. However, our patient presented no MDS features on repeated bone marrow examination and on cytogenetic analysis. Regardless to all our data, we concluded that our patient present the first case ever reported of chronic non spherocytic anemia related to an acquired somatic mutation of the G6PD gene at the level of a hematopoietic pluripotent cell. Disclosures: No relevant conflicts of interest to declare.
AbstractA glucose-6-phosphate dehydrogenase (G6PD) variant was studied in a mulatto patient with chronic nonspherocytic hemolytic anemia. This variant has reduced activity, increased thermolability, a reduced Michaelis constant for glucose-6-phosphate,slightly increased electrophoretic mobility, a biphasic pH activity profile, high 2-deoxyglucose-6-phosphate utilization, normal diamino nicotinamide adenine dinucleotide phosphate utilization and a peak of elution profile after G6PD B. The electrophoretic, kinetic,and chromatographic properties of this erythrocyte G6PD variant allow the conclusion that G6PD Varadero is probably a new variant.
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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