DeCure for Hereditary hyperferritinemia with congenital cataracts
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary hyperferritinemia with congenital cataracts — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary hyperferritinemia with congenital cataracts maps to a 13-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 hereditary hyperferritinemia with congenital cataracts 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
crystallin gamma D (CRYGD) — CRYGD 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 mnbdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9G3W · 1.8 Å · ligand 5-MERCAPTO-2-NITRO-BENZOIC ACID (MNB). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disease caused by mutations in the FTL gene. It produces bilateral paediatric cataract and hyperferritinemia without iron overload. A 2023 case series of three Brazilian families, involving eleven individuals, found the likely pathogenic variant c.-157G>A in FTL in all affected members. They presented slowly progressing bilateral cataract symptoms before age 14, with varied bilateral diffuse opacities. Hyperferritinemia ranged from 971 ng/mL to 4899 ng/mL. Two affected individuals also carried a pathogenic variant in HFE (c.187C>G, p.H63D) and had the highest serum ferritin values in that cohort; the authors note that few publications describe individuals with mutations in both FTL and HFE, and further studies are needed.
A 2010 abstract describes a healthy 42-year-old white male with serum ferritin of 1800 ng/mL and early-onset cataracts, whose sibling had undergone unnecessary management for hemochromatosis. The abstract states that confirmation of genetic testing does not change management, that the only intervention is ophthalmologic, and that HHCS is a benign condition requiring avoidance of increased healthcare costs. It notes that patients tolerate phlebotomies poorly and will develop iron deficiency anaemia. The triad of cataract, asymptomatic patient, and hyperferritinemia should prompt recognition to prevent worthless and costly investigations.
Broader context from a 2021 Danish chart review of 211 children with bilateral cataracts found that 29.4% had hereditary cataracts, and a genetic cause was demonstrated in 74 children. Systemic comorbidities were very common. Genetic work-up provided a diagnosis with therapeutic consequences in some patients where systemic disease would have caused irreversible damage if untreated. A 2020 review notes that 115 genes have been associated with syndromic and non-syndromic cataract, and 38 disease-causing genes for isolated cataract have been identified.
What is still missing: no controlled trials of any pharmacological intervention for HHCS exist; the evidence base consists entirely of case series and retrospective reviews. There is no data on whether any drug can lower ferritin or alter cataract progression in HHCS. Patient stratification by concurrent HFE mutations remains speculative. Funding for a prospective natural history study or a trial of iron chelation or other repurposed agents has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Ophthalmology · 2020 · 85 citations · open access
AbstractCataract is the most common cause of blindness in the world; during infancy and early childhood, it frequently results in visual impairment. Congenital cataracts are phenotypically and genotypically heterogeneous and can occur in isolation or in association with other systemic disorders. Significant progress has been made in identifying the molecular genetic basis of cataract; 115 genes to date have been found to be associated with syndromic and non-syndromic cataract and 38 disease-causing genes have been identified to date to be associated with isolated cataract. In this review, we briefly discuss lens development and cataractogenesis, detail the variable cataract phenotypes and molecular mechanisms, including genotype-phenotype correlations, and explore future novel therapeutic avenues including cellular therapies and pharmacological treatments.
Ophthalmic Genetics · 2021 · 15 citations · open access
Genetic disease is a common cause of bilateral childhood cataract in Denmark
AbstractPurpose: Bilateral childhood cataracts can be caused by a metabolic disease, constitute a part of a syndrome, run in families, be sporadic or iatrogenic. The amount of work-up needed to establish a cause is discussed and the aim of the present study was to evaluate causes of bilateral childhood cataract.Methods: Chart review of 211 Danish children with bilateral cataracts. Information on work-up was retrieved with special focus on general health, metabolic screening, evaluation for congenital infections and genetic testing.Results: Cataract was seen in combination with systemic disease in 40.8%, 29.4% had hereditary cataracts, 27.0% had isolated cataract, in 1.4% it was associated with ocular malformations and 1.4% had been born prematurely without any other sequelae than the cataract. A genetic cause could be demonstrated in 74 children.Conclusion: Systemic comorbidities are very common in children with cataract and are not always known prior to the diagnosis of cataract. Genetic evaluation, especially targeted analyses, provided a molecular genetic diagnosis in a large proportion of those tested but it also failed to provide a molecular genetic diagnosis in some patients with a family history suggesting autosomal dominant inheritance. Most importantly, in some patients, genetic work-up provided a diagnosis in patients where it had therapeutic consequences and where the systemic disease would have caused irreversible damage, had it not been treated timely. Given the high prevalence of systemic disease, it seems advisable to co-manage children with bilateral cataracts with a pediatrician and to include genetic evaluation as part of the work-up.
International Journal of Molecular Sciences · 2023 · 6 citations · open access
Genotypic–Phenotypic Correlations of Hereditary Hyperferritinemia-Cataract Syndrome: Case Series of Three Brazilian Families
AbstractHereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis—a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.
AbstractAbstract Abstract 5154 A healthy 42y/o, White, male, without any systemic illnesses or complaints presents with a serum ferritin of 1800ng/mL; the discrepancy between his optimal physical status and the laboratory result, poses a challenge to the most astute clinician. The fundamental goal of this abstract is to provide recognition and prevention to torment that patients with Hereditary Hyperferritinemia Cataract Syndrome (HHCS) are exposed to. The history will offer an important clue, of early onset cataracts. Our patient was guided by an older sibling who herself for many years underwent unnecessary clinical management for hemochromatosis. The presence of hereditary hyperferritinemia cataract syndrome (HHCS) has been defined in families all across the world and likely is under-diagnosed. Such a rare syndrome may never make it into a hematology practice and be missed while the focus is on the “panic” ferritin result. Our patient is part of a family who has had the syndrome since at least the mid 1800's. The scope of this disorder is bringing to reality that confirmation of genetic testing doesn't change management and that the only intervention will be ophthalmologic. The abundant testing for ferritin across medical specialties may cause a rise in HHCS cases, recognizing this syndrome early on will lead to protect patients from insistent and costly interventions. These patients tolerate poorly phlebotomies and will develop iron deficiency anemia. Although appropriate data is available regarding HHCS there is no relevant clinical data to support a poor clinical outcome, and the precise recognition this triad (cataract, asymptomatic patient and hyperferritinemia) will avoid worthless and costly investigations. In this case, a family member who was victimized by excessive workup, was able to research, discover the family mutation and offer this practitioner the tools towards practicing better patient care. In summary, Hereditary Hyperferritinemia Cataract Syndrome is a benign condition that requires avoidance of increased healthcare costs for the proband. Disclosures: No relevant conflicts of interest to declare.
Anales del Sistema Sanitario de Navarra · 2008 · 0 citations · open access
Hereditary syndrome of hyperferritinemia and cataract
AbstractThis report describes a family with hereditary hyperferritinemia cataract syndrome. Inheritance is autosomal dominant and clinical characteristics of this syndrome are familial cataracts of early development and elevated serum ferritin levels but otherwise normal iron studies and haematological parameters. It is important to increase awareness of this entity in order to diagnose new cases and avoid unnecessary diagnostic tests and inadequate treatments.
Journal of Current Hematology & Oncology Research · 2023 · 0 citations · open access
Hereditary hyperferritinemia cataract syndrome with iron deficiency : a case report
AbstractHereditary hyperferritinemia-cataract syndrome (HHCS) is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. HHCS is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. In this case report, we aimed to present a young female patient with a history of cataracts in herself and her family members. Our patient had the dilemma of iron deficiency anemia and hyperferritinemia. As in our patient, patients with HHCS apply to many outpatient clinics and have difficulty in diagnosis. For this reason, we prepared our case to raise awareness.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
