DeCure for Thiamine-responsive megaloblastic anemia syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thiamine-responsive megaloblastic anemia 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 moduleThiamine-responsive megaloblastic anemia 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
approvedThiamineApproved drug
Structures already discussed alongside thiamine-responsive megaloblastic anemia syndrome in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of mouse thiamine triphosphatase — Thiamine has a real, experimentally solved structure in complex with this target (PDB 5A64, 2.1 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet v4edrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5A64 · 2.1 Å · ligand Thiamine (V4E). Experimental structure, not a prediction.
What the evidence adds up to
Thiamine-responsive megaloblastic anemia syndrome is an autosomal recessive disorder caused by mutations in the SLC19A2 gene, which encodes a high-affinity thiamine transporter. The syndrome is characterised by a triad of megaloblastic anemia, sensorineural deafness, and diabetes mellitus, with some patients also showing thrombocytopenia, leukopenia, retinopathy, or patent ductus arteriosus. In a 2017 report of three siblings with a homozygous c.454delGGCATinsAT mutation, the index case presented at 14 months with severe non-ketotic hyperglycemia and required insulin; two siblings were started on thiamine before diabetes developed. One of those siblings developed transient hyperglycemia after several years on 12 mg/kg thiamine, which resolved when the dose was increased to 23 mg/kg. The younger sibling remained diabetes-free on 24 mg/kg thiamine. The authors concluded that thiamine appeared to affect pancreatic beta cell function in TRMA, given the resolution of impaired fasting glucose with higher doses and the absence of diabetes in early-treated siblings.
In a 2002 case report, a five-year-old boy with TRMA was described, and the authors noted that pharmacological doses of thiamine ameliorated both the megaloblastic anemia and diabetes mellitus. A 2012 report from Kashmir described a six-year-old girl whose diabetes remitted after thiamine replacement; her megaloblastic anemia also responded to high doses of thiamine. A 2018 case report of a two-year-old girl stated that her anemia improved after thiamine 100 mg once daily, and her fasting blood sugar fell into the normal range. A 2020 report described a 19-year-old man with known TRMA who presented with bicytopenia (haemoglobin 5.4 g/dL, platelets 38×10⁹/L) after his thiamine treatment had been discontinued for three months during COVID-19 confinement. Parenteral thiamine 100 mg daily restored haematopoiesis within three weeks.
Despite these reports, the evidence base remains limited to small case series and individual case reports. There are no controlled trials comparing thiamine doses or schedules, no long-term data on optimal dosing for preventing diabetes or hearing loss, and no prospective studies that stratify patients by mutation type or age at treatment initiation. The natural history of the syndrome under sustained thiamine therapy is not well characterised, and the degree to which thiamine can prevent or reverse sensorineural deafness is not established. What is missing is systematic, multi-centre data collection, standardised outcome measures, and funding for a prospective registry or trial that could determine whether early, high-dose thiamine consistently preserves beta cell function and haematological stability across the full range of SLC19A2 mutations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pediatric Diabetes · 2002 · 56 citations
TRMA syndrome (thiamine-responsive megaloblastic anemia): a case report and review of the literature
AbstractThiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder with features that include megaloblastic anemia, mild thrombocytopenia and leukopenia, sensorineural deafness and diabetes mellitus. In this disease, the active thiamine uptake into cells is disturbed. Treatment with pharmacological doses of thiamine ameliorates the megaloblastic anemia and diabetes mellitus. Previous studies have demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter. We present a 5-yr-old-boy with TRMA and, because of its rarity, we review the literature.
Journal of Tropical Pediatrics · 2008 · 16 citations · open access
A Novel Mutation in the SLC19A2 Gene in a Turkish Female with Thiamine-responsive Megaloblastic Anemia Syndrome
AbstractReported here is a 2-year-old girl who was diagnosed to have thiamine-responsive megaloblastic anemia during evaluations for her bilateral neurosensorial deafness. Besides reporting a new mutation on the gene SLC19A2 for the first time in the literature, we highlight the recognition of this syndrome--when megaloblastic anemia and diabetes mellitus coexists--and the role of thiamine replacement for the treatment of both disorders.
Journal of Pediatric Endocrinology and Metabolism · 2017 · 14 citations
Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation
AbstractThree siblings with thiamine-responsive megaloblastic anemia (TRMA) with a homozygous c.454delGGCATinsAT mutation in SLC19A2 are described. The index case presented at 14 months' old with severe non-ketotic hyperglycemia, dehydration, seizures and sinovenous thrombosis. She was started on insulin and developed sensorineural hearing loss around 2 years old. Two siblings were found to have the same mutation and were started on thiamine. One sibling developed transient hyperglycemia after several years of thiamine supplementation of 12 mg/kg that resolved with an increased thiamine dose (23 mg/kg). A younger sibling continues to remain diabetes-free on thiamine (24 mg/kg). The clinical course in this family suggests that there is an effect of thiamine on pancreatic beta cell function in patients with TRMA given the resolution of impaired fasting glucose with increasing thiamine dose in one sibling and the lack of diabetes to date in the siblings that were treated early with thiamine.
Indian Journal of Endocrinology and Metabolism · 2012 · 9 citations · open access
Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent
AbstractThiamine responsive megaloblastic anemia syndrome, an autosomal recessive inherited disorder characterized by a triad of anemia, diabetes mellitus and sensorineural deafness is caused by a deficiency of a thiamine transporter protein. The disorder is rare and has not been reported from our community which has high background of consanguinity. We report a six years old girl who presented with diabetes mellitus which remitted after thiamine replacement. The girl in addition had sensorineural deafness, reinopathy, atrial septal defect and megaloblastic anemia which responded to high doses of thymine. This is the first case reported from Kashmir valley and third from India. The presentation and management in such cases is discussed.
Journal of College of Physicians And Surgeons Pakistan · 2018 · 2 citations
Thiamine Responsive Megaloblastic Anaemia, Diabetes Mellitus And Sensorineural Hearing Loss In A Child
AbstractThiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive inherited disorder characterised by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. We report a case of 2-year-old girl whose anemia improved following administration of thiamine. She came with the history of persistent anaemia for the last one year. Anaemia was not responding to iron, vitamin B12, and folate replacement therapy. The bone marrow aspiration revealed hypercellular marrow with megaloblastic changes and more than 15% ring sideroblasts. The hearing assessment revealed sensorineural hearing loss. Blood sugar random and HBA1c was raised. Final diagnosis of TRMA was made. She was started on thiamine 100 mg OD, with normal routine balanced diet. She responded very well to thiamine. Her haemoglobin improved and blood sugar fasting came down in normal range. This case report sensitises the early diagnosis, and treatment with thiamine in children presenting with anemia, diabetes and deafness.
Pan African Medical Journal · 2020 · 1 citations · open access
Relapse of rare diseases during COVID-19 pandemic: bicytopenia in an adult patient with thiamine-responsive megaloblastic anaemia (TRMA)
AbstractThiamine-responsive megaloblastic anaemia (TRMA) is a syndrome associated with megaloblastic anaemia, diabetes mellitus and sensorineural deafness, due to mutations in the SLC19A2 gene, which codes for a thiamine carrier protein. Oral thiamine supplementation is the main treatment. We report the case of a 19-year-old man known for TRMA, who presented in the emergency department with bicytopenia (haemoglobin 5,4 g/dL, thrombocytes 38×109/L) revealed by dyspnea and chest pain. Investigations excluded bleeding, hemolysis, coagulopathy and iron deficiencies. A recent infection and an acute coronary syndrome have also been eliminated. We later found out that thiamine treatment had been discontinued three months before, due to general confinement in Tunisia during the COVID-19 pandemic. Parenteral administration of 100 mg of thiamine daily resulted in the recovery of haematopoiesis within three weeks.
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.
