DeCure for Hyperinsulinemic hypoglycemia, familial, 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperinsulinemic hypoglycemia, familial, 1 — 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 moduleHyperinsulinemic hypoglycemia, familial, 1 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 hyperinsulinemic hypoglycemia, familial, 1 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
ATP binding cassette subfamily C member 8 (ABCC8) — ABCC8 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6C3O · 3.9 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Persistent hyperinsulinemic hypoglycemia of infancy is rare in outbred communities (about 1 per 50,000 persons) but reaches about 1 per 2,500 in inbred Arabic communities with an autosomal recessive form. Some patients respond to diazoxide or somatostatin, but others require partial pancreatectomy. One case report describes a patient maintained on diazoxide for 4.5 years with normoglycemia and no side effects including hypertrichosis. Another report notes that long-term diazoxide and somatostatin analogues have been used despite some side effects.
Mutations in at least 16 genes are implicated, including ABCC8, GLUD1, GCK, HNF4A, HNF1A, and PMM2. A novel homozygous p.L171F mutation in ABCC8 caused severe diffuse hyperinsulinemic hypoglycemia that was diazoxide-unresponsive and required surgery; the same patient later evolved to complete insulin-deficient, sulfonylurea-responsive diabetes, the first reported homozygous ABCC8 mutation with that progression. The authors emphasise that patients with neonatal hyperinsulinemic hypoglycemia due to ABCC8 mutations, especially those managed medically, need long-term follow-up for risk of later diabetes. A familial case of GLUD1 mutation presented with protein-induced hyperinsulinemic hypoglycemia and hyperammonemia, which cannot be detected by standard fasting glucose testing and requires a protein load test.
A third known patient with congenital disorder of glycosylation type Id (CDG-Id) presented with hyperinsulinemic hypoglycemia and islet cell hyperplasia with increased beta-cell mass at autopsy. The patient carried a novel homozygous 512G>A mutation in hALG3, died at 19 days of age, and also had Dandy-Walker malformation, facial dysmorphisms, and profound hypotonia. Lentiviral complementation with wild-type hALG3 corrected the biochemical defect in the patient's fibroblasts. The authors conclude that CDG should be ruled out in persistent hyperinsulinemic hypoglycemia of unknown cause.
What remains missing is a standardised diagnostic and therapeutic algorithm that can be applied across the many genetic subtypes, and prospective data on how often medically managed patients later develop diabetes. The 2010 paper notes that highly specialised examinations for etiological diagnosis, treatment, prognosis, and genetic counselling require a well-trained multidisciplinary team, but no large-scale trial or registry has yet been funded to stratify patients by mutation and long-term outcome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1997 · 222 citations · open access
Familial Persistent Hyperinsulinemic Hypoglycemia of Infancy and Mutations in the Sulfonylurea Receptor
Abstract[1st paragraph] Persistent hyperinsulinemic hypoglycemia of infancy is caused by inappropriate and excessive secretion of insulin. Although the disease is rare in outbred communities (approximately 1 case per 50,000 persons), the incidence is approximately 1 per 2500 in inbred Arabic communities in which there is a familial (autosomal recessive) form of the disease. The disease most commonly presents with severe hypoglycemia a few hours after birth, although some cases present after several weeks or months. Some patients have a response to treatment with diazoxide or somatostatin, but others require partial pancreatectomy to control the hyperinsulinism.
The Journal of Clinical Endocrinology & Metabolism · 2005 · 100 citations · open access
Congenital Disorder of Glycosylation Id Presenting with Hyperinsulinemic Hypoglycemia and Islet Cell Hyperplasia
AbstractCONTEXT: Inborn errors in protein glycosylation, such as the congenital disorders of glycosylation (CDGs), generate multifaceted syndromes that impair many organ systems. We here report the diagnosis of the third known patient with CDG-Id. RESULTS: The patient's phenotype was extremely severe, and she succumbed at 19 d of age. Leading features included hyperinsulinemic hypoglycemia, and autopsy revealed islet cell hyperplasia with increased beta-cell mass. Other features were a Dandy-Walker malformation, facial dysmorphisms, and profound hypotonia. The patient carried a novel homozygous point mutation (512G>A) in the hALG3 gene, which encodes a mannosyltransferase. Lentiviral complementation with wild-type hALG3 corrects the biochemical defect in the patient's fibroblasts. CONCLUSIONS: Our findings underscore the importance of proper glycosylation in several major organ systems and emphasize that CDG should be ruled out in patients with persistent hyperinsulinemic hypoglycemia of unknown etiology.
Diabetes Metabolic Syndrome and Obesity · 2024 · 4 citations · open access
Genetic Variations in Hyperinsulinemic Hypoglycemia: Active versus Inactive Mutations
AbstractAbstract: Hyperinsulinemic Hypoglycemia (HH) is a rare condition that affects newborn children in the postnatal period, represented by dangerously low levels of blood glucose in a persistent manner, which puts the baby at high risk of multiple issues, especially regarding the brain cells if the baby does not take the appropriate medication or have the correct diagnosis. Hyperinsulinemic Hypoglycemia can happen due to an active or inactive mutation in 16 genes responsible for glucose metabolism and insulin secretion ( GLUD1 , GCK , SLC16A1 , HK1 , CACNA1D , KCNJ11 , ABCC8 , FOXA2 , HNF1A , HNF4A , HADH , PGM1 , UCP2 , KCNQ1 , PMM2 , EIF2S3 ). These mutations can take place in many forms, either defused or local, affecting several or all pancreatic beta cells respectively. This review summarizes genetic variations diagnosis and treatment of Hyperinsulinemic Hypoglycemia. Keywords: Hyperinsulinemic Hypoglycemia, nesidioblastosis, GLUD1 , hexokinase , FOXA2
Journal of Pediatric Endocrinology and Metabolism · 1997 · 4 citations
Long-Term Diazoxide Treatment in Persistent Hyperinsulincmic Hypoglycemia of Infancy: A Case Report
AbstractLong-term diazoxide and somatostatin analogue have been used in the treatment of persistent hyperinsulinemic hypoglycemia of infancy albeit with some side effects. We report a case with persistent hyperinsulinemic hypoglycemia who has been on diazoxide therapy for 4.5 years. Diazoxide treatment maintained normoglycemia without causing any side effects, including hypertrichosis.
Journal of Clinical Research in Pediatric Endocrinology · 2018 · 4 citations · open access
Congenital hyperinsulinism and evolution to sulfonylurea-responsive diabetes later in life due to a novel homozygous p.L171F ABCC8 mutation
AbstractHomozygous ABCC8 mutations cause severe persistent diffuse hyperinsulinemic hypoglycaemia (HH) which is usually diazoxide unresponsive and requires surgical therapy. In medically managed patients with congenital hyperinsulinism (CHI), disease symptoms become milder overtime. Hyperinsulinemic hypoglycemia at neonatal period and later diabetes have been reported in heterozygous mutation of HNF4A and HNF1A as well as heterozygous ABCC8 mutations What this study adds? We describe the first homozygous ABCC8 mutation with HH at neonatal period and evolution to complete insulin deficient, sulphonylurea responsive diabetes mellitus. Findings from present work which show a broad range of clinical spectrum from asymptomatic, mild symptomatic hypoglycemia, severe hypoglycemia as well as insulin deficient diabetes mellitus in family members with identical mutation confirms the phenotypical variations in ABCC8 mutations Present case report emphasizes the need for long-term follow up of patients with HH at neonatal period due to ABCC8 mutations, particularly those managed with medical therapy for risk of developing diabetes in later life.
Hyperinsulinemic Hypoglycemias in Infancy and Childhood - Diagnostic Therapeutic Algorithm with Contribution of Two Cases
AbstractHypoglycemia is not an independent diagnosis. It is a pathophysiological syndrome whose cause needs to be identified. Identifying it is just the first step to making the diagnosis as precisely as possible and to preventing brain damage. Timely diagnosis and treatment are factors of paramount importance for the prognosis of affected patients. The aim of this study was to present two of our patients with hyperinsulinemic hypoglycemia because of the rarity of the condition and to propose a diagnostic-therapeutic algorithm of hypoglycemic syndrome in childhood. Identifying the genetic mutations using DNA analysis for both children enabled us to determine the prognosis and to provide genetic counseling about the next pregnancies in the affected families. We make a detailed classification of different types of hypoglycemia and the various therapeutic modalities: dietary, medicinal and surgical depending on the etiology. It is concluded that the highly specialized examinations which ensure the etiological diagnose, treatment, prognosis and genetic consultation demand the participation of a well trained medical team--both in the clinical division and in the laboratory.
Problems of Endocrinology · 2017 · 1 citations · open access
Familial case of congenital hyperinsulinism associated with mutation in the GLUD1 gene
AbstractCongenital hyperinsulinism (CHI) is a rare hereditary disease characterized by hypoglycemia in children during the first year of life. Late diagnosis and inadequate therapy may result in severe neurological complications. Mutations in the GLUD1 gene that encodes glutamate dehydrogenase are one of the causes of CHI. This form of CHI is characterized by protein-induced hyperinsulinemic hypoglycemia and hyperammonemia in patients. Diagnosing can be challenging because hyperinsulinemic hypoglycemia cannot be detected using the conventional fasting glucose test. Extensive examination including the protein load test is needed to refine diagnosis. We report a familial case where the mother and two daughters were diagnosed with CHI and had a mutation in the catalytic domain of the GLUD1 gene. The clinical presentation, the laboratory data, the outcome of therapy, and the dynamic follow up data for the patients are presented.
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.
