DeCure for Cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCirrhosis - dystonia - polycythemia - hypermanganesemia syndrome maps to a 1-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 cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome 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
solute carrier family 30 member 10 (SLC30A10) — SLC30A10 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9KVX · 2.79 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC) is a rare autosomal recessive disorder caused by mutations in the SLC30A10 gene, which encodes a manganese transporter. Manganese accumulates in the brain, liver, and muscles, leading to generalised dystonia, polycythemia, and liver cirrhosis. Two siblings with a novel SLC30A10 mutation showed characteristic hyperintensity on T1-weighted noncontrast neuroimaging, and the authors note the condition is treatable, though they do not specify which treatment was used or give numerical outcomes. A separate report of a 2½-year-old girl with lower limb weakness and difficulty walking for six months found deranged laboratory values and elevated manganese; she received six cycles of EDTA therapy, which produced improvement in her condition, but no response rates or survival data are provided.
A 19-year-old female with a homozygous pathogenic SLC30A10 variant presented with longstanding polycythemia identified in childhood, fatigue, reduced appetite, and chronic joint pain, but had an unremarkable neurological examination. This case highlights diagnostic and therapeutic challenges in managing systemic features of the disorder. In a consanguineous Saudi family with two affected individuals showing severe motor impairment, spastic paraparesis, postural instability, and dystonia, whole exome sequencing identified a recurrent homozygous missense variant (c.266T>C; p.L89P) in SLC30A10, which bioinformatics tools predicted as potentially pathogenic and highly conserved in vertebrates.
The evidence is limited to small case reports and a single family study, with no controlled trials. EDTA therapy showed improvement in one child, but no quantitative outcomes, long-term follow-up, or comparative data exist. What is still missing are larger patient cohorts, standardised treatment protocols, and prospective studies that stratify by mutation type, age at treatment, and severity of hepatic or neurological involvement. Funding for natural history studies and clinical trials of chelation or other manganese-lowering strategies 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.
Journal of Pediatric Genetics · 2020 · 1 citations · open access
Treatable Hereditary Manganese Transport Disorder: Novel SLC30A10 Mutation and its Characteristic Neuroimaging Appearance in Two Siblings
AbstractHypermanganesemia with dystonia and polycythemia along with liver cirrhosis is a rare syndromic complex that is associated with a characteristic genetic mutation and a typical appearance in the T1-weighted noncontrast image. In this article, we reported the neuroimaging findings of two siblings affected by this syndrome. There are few reported cases in literature with similar findings. Diagnosing this problem will help in improving the outcomes as the condition is treatable. We reviewed the clinical and imaging findings of this condition and the differential diagnosis related to it.
Greater South Information System · 2022 · 0 citations · open access
Hypermanganesaemia with dystonia polycythemia and cirrhosis
AbstractHypermanganesaemia with dystonia, polycythemia, and cirrhosis (HMDPC) is a rare genetic and autosomal recessive disorder that occurs due to mutation of the SLC3A10 gene, which encodes the manganese (Mn) transporter in the body; as a result, Mn accumulates in the brain, liver and muscles. This accumulation leads to symptoms of generalized dystonia, polycythemia, and hypermanganesaemia. In this report, we present the case of a 2½-year-old baby girl (patient) with complaints of lower limb weakness and increased difficulty in walking for six months. Her laboratory test results showed deranged values with increased Mn levels in the body. The patient was put on six cycles of EDTA therapy, which showed an improvement in her condition. This case report is presented to create awareness about a rare genetic disorder with an effective treatment in some cases. Thus, more work and research is required to understand and develop better treatment options for this disease.
Greater South Information System · 2022 · 0 citations · open access
Hypermanganesaemia with dystonia polycythemia and cirrhosis
AbstractHypermanganesaemia with dystonia, polycythemia, and cirrhosis (HMDPC) is a rare genetic and autosomal recessive disorder that occurs due to mutation of the SLC3A10 gene, which encodes the manganese (Mn) transporter in the body; as a result, Mn accumulates in the brain, liver and muscles. This accumulation leads to symptoms of generalized dystonia, polycythemia, and hypermanganesaemia. In this report, we present the case of a 2½-year-old baby girl (patient) with complaints of lower limb weakness and increased difficulty in walking for six months. Her laboratory test results showed deranged values with increased Mn levels in the body. The patient was put on six cycles of EDTA therapy, which showed an improvement in her condition. This case report is presented to create awareness about a rare genetic disorder with an effective treatment in some cases. Thus, more work and research is required to understand and develop better treatment options for this disease.
Journal of Applied Hematology · 2025 · 0 citations · open access
Polycythemia and Systemic Manifestations in a 19-year-old Female with SLC30A10 Mutation
AbstractAbstract This report presents the case of a 19-year-old female with longstanding polycythemia identified in childhood and systemic symptoms, including fatigue, reduced appetite, and chronic joint pain. Neurological examination was unremarkable. Genetic testing revealed a homozygous pathogenic variant in the SLC30A10 gene, consistent with hypermanganesemia with dystonia. This condition, an autosomal recessive disorder, typically involves hematological, neurological, and hepatic systems. This case highlights the diagnostic and therapeutic challenges associated with managing systemic features in patients with SLC30A10 mutations.
Journal of Clinical Medicine · 2024 · 0 citations · open access
Exome Sequence Analysis to Characterize Undiagnosed Family Segregating Motor Impairment and Dystonia
AbstractBackground: Hypermanganesemia with dystonia 1 (HMNDYT1) is a rare genetic disorder characterized by elevated blood manganese levels. This condition is associated with polycythemia, motor neurodegeneration with extrapyramidal features, and hepatic dysfunction, which can progress to cirrhosis in some patients. Materials and Methods: In this study, a consanguineous Saudi family with two affected individuals exhibiting symptoms of severe motor impairment, spastic paraparesis, postural instability, and dystonia was studied. Clinical and radiographic evaluations were conducted on the affected individuals. Whole exome sequencing (WES) was performed to diagnose the disease and to determine the causative variant underlying the phenotype. Moreover, Sanger sequencing was used for validation and segregation analysis of the identified variant. Bioinformatics tools were utilized to predict the pathogenicity of candidate variants based on ACMG criteria. Results: Exome sequencing detected a recurrent homozygous missense variant (c.266T>C; p.L89P) in exon 1 of the SLC30A10 gene. Sanger sequencing was employed to validate the segregation of the discovered variant in all available family members. Bioinformatics tools predicted that the variant is potentially pathogenic. Moreover, conservation analysis showed that the variant is highly conserved in vertebrates. Conclusions: This study shows that exome sequencing is instrumental in diagnosing undiagnosed neurodevelopmental disorders. Moreover, this study expands the mutation spectrum of SLC30A10 in distinct populations.
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.
