AnatomyDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesNamed Groups
Congenital HyperinsulinismHyperinsulinismSulfonylurea ReceptorsReceptors, DrugPotassium Channels, Inwardly RectifyingDiazoxidePancreatectomyATP-Binding Cassette TransportersKATP ChannelsHypoglycemiaGlutamate DehydrogenaseInsulinPotassium ChannelsInsulin-Secreting CellsInfant, NewbornMutationMutation, MissenseHeterozygoteDiagnostic Techniques, EndocrineHyperammonemia
Children's Hospital ofHypoglycemia due to congenital hyperinsulinismHyperinsulinemic hypoglycemiaKATPGlucoseHuman pancreaticInfantsDiffuseSevereGenesMutationsABCC8HereditaryPersistentHypoglycaemiaHistologyCHOPIsletOccurPaternal uniparental disomyAdultsDisorderTransientGlucagonConcomitantSpontaneousPediatricPUPDDisordersChildrenDiazoxideKCNJ11OvarianMedicallyTreatmentsDiseasesSeverityIndividualsSymptomsTissueTypesGeneTreatmentMolecularTypicallyExcessive insulinBloodDefects
Children's Hospital of5
  • Even today with all we know, that's the frequency," said De León, chief of the Division of Endocrinology and Diabetes and director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia (CHOP). (medscape.com)
  • A center within the Children's Hospital of Philadelphia that specializes in the treatment of hyperinsulinism in children. (jscreen.org)
  • The Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia is working on a research study to better understand how people with hyperinsulinism may have different blood sugar responses to certain tests (like fasting or drinking a high-protein shake) when compared to people without hyperinsulinism. (chop.edu)
  • Since October 1998 the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia has evaluated and treated more than 400 patients - making it the largest program of its kind in North America. (chop.edu)
  • At The Children's Hospital of Philadelphia Hyperinsulinism Center, we see approximately two-thirds of all the cases that are born in this country with hyperinsulinism. (chop.edu)
Hypoglycemia due to congenital hyperinsulinism1
Hyperinsulinemic hypoglycemia2
KATP6
  • Congenital hyperinsulinism is a condition of dysregulated insulin secretion often caused by inactivating mutations of the ATP-sensitive K+ (KATP) channel in the pancreatic β cell. (jci.org)
  • In contrast to a previous report of increased diabetes risk in dominant KATP hyperinsulinism, only 4 of 29 adults had diabetes. (jci.org)
  • These data highlight distinctive features of dominant KATP hyperinsulinism relative to the more common and more severe recessive form, including retention of normal subunit trafficking, impaired channel activity, and a milder hypoglycemia phenotype that may escape detection in infancy and is often responsive to diazoxide medical therapy, without the need for surgical pancreatectomy. (jci.org)
  • Patients with CHI frequently have mutations in the ABCC8 and KCNJ11 genes, which code for KATP channels in pancreatic beta cells. (eurospe.org)
  • Update of variants identified in the pancreatic ß-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. (uchicago.edu)
  • The pancreatic -cell ATP-sensitive potassium (KATP) channel is a multimeric protein complex made up of four inwardly rectifying potassium channel (Kir6. (thetechnoant.info)
Glucose8
  • To compensate for the increased blood glucose levels, fetal pancreatic beta cells can undergo hyperplasia. (wikipedia.org)
  • Background and Objective: Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. (eurospe.org)
  • In part 2 of the trial, being 21 days open-label treatment, 10 of the 12 neonates and infants weaned off intravenous glucose for at least 12 hours and 7 of the 12 neonates and infants remained weaned off intravenous glucose at the end of the trial without concomitant pancreatic surgery. (biotech-365.com)
  • If a child shows symptoms of ABCC8-related hyperinsulinism at birth, intravenous glucose is often given to raise and stabilize the blood sugar level. (jscreen.org)
  • Children that have hyperinsulinism produce too much insulin and that causes severe low blood glucose. (chop.edu)
  • Hyperinsulinism can be associated with several types of medical problems, which can be roughly divided into two broad and largely non-overlapping categories: those tending toward reduced sensitivity to insulin and high blood glucose levels ( hyperglycemia ), and those tending toward excessive insulin secretion and low glucose levels ( hypoglycemia ). (ipfs.io)
  • Insulin levels above 3 μU/mL are inappropriate when the glucose level is below 50 mg/dL (2.8 mM), and may indicate hyperinsulinism as the cause of the hypoglycemia. (ipfs.io)
  • They are essential for glucose-stimulated insulin secretion from pancreatic beta-cells, contribute to the mechanisms by which hypoglycaemia stimulates glucagon release from pancreatic alpha-cells, and are involved in glucose uptake into skeletal muscle, glucose production and release from the liver, and feeding behaviour. (ox.ac.uk)
Human pancreatic1
  • Importantly, hallmark functions of human pancreatic β cells improve in the years after birth. (einsteinmed.edu)
Infants7
Diffuse4
Severe6
  • The most common and severe form of congenital hyperinsulinism is due to inactivating mutations of two genes that encode subunits of the beta-cell K ATP channel, leading to dysregulated insulin secretion. (medscape.com)
  • [ 5 ] Severe cases of congenital HI may be unresponsive to either diazoxide or octreotide and require intensive management with tube feedings, near-total pancreatectomy, or partial pancreatectomy. (medscape.com)
  • In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. (lu.se)
  • Congenital hyperinsulinism (CHI) is a rare hereditary condition that causes excessive insulin production in the clinical picture of severe hypoglycemia. (eurospe.org)
  • Neonatal hypoglycaemia can be transient and yet pose a significant risk of neuroglycopaenia, especially with severe and recurrent hypoglycaemia in Congenital Hyperinsulinism. (eurospe.org)
  • Background: Congenital Hyperinsulinism (CHI) is the most common cause of recurrent and severe hypoglycaemia in childhood and can be broadly categorised into two subtypes. (eurospe.org)
Genes4
  • Inactivating mutations of the ABCC8 and KCNJ11 genes, which are located on 11p15.1 and encode the SUR1 and Kir6.2 subunits of the pancreatic β-cell ATP-sensitive potassium channel (K ATP channel) respectively, are the most common genetic aetiology of HI [ 1 ]. (biomedcentral.com)
  • Other genes have been identified which also cause hyperinsulinism. (jscreen.org)
  • Certain genes may play a role in congenital heart disease. (pharmaceuticalintelligence.com)
  • Not surprisingly, loss- or gain-of-function mutations in K(ATP) channel genes have profound effects, giving rise to congenital hyperinsulinaemia and neonatal diabetes respectively. (ox.ac.uk)
Mutations4
  • A rare disorder, occurring in 1 in 20,000 to 1 in 50,000 US live births, congenital hyperinsulinism is caused by several different genetic mutations. (medscape.com)
  • One drug, diazoxide, is a K ATP channel agonist that suppresses insulin release in some types of hyperinsulinism but not in the majority of patients who have those two particular K ATP channel mutations. (medscape.com)
  • A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1. (exeter.ac.uk)
  • We demonstrated that these mutations resulted in expression of HK1 in the pancreatic beta-cells causing inappropriate insulin secretion and congenital hyperinsulinism. (exeter.ac.uk)
ABCC813
Hereditary1
  • Patient education Genetic testing for hereditary breast, ovarian, prostate, and pancreatic cancer (Beyond the basics). (genepowerx.com)
Persistent3
Hypoglycaemia2
Histology2
  • The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. (lu.se)
  • However, pancreatic histology revealed atypical findings of coalescing nests and trabeculae of adenomatosis scattered with islets with isolated enlarged, hyperchromatic nuclei scattered throughout the pancreas. (biomedcentral.com)
CHOP1
  • Significant breakthroughs in pancreatic care have happened right here at CHOP, and we are Accredited by the National Pancreas Foundation (NPF) as a Clinical Center of Excellence for the treatment of pediatric pancreatitis. (chop.edu)
Islet3
  • Congenital Hyperinsulinism (CHI) is primarily associated with defects in the regulated release of insulin from ß-cells but little information is available about the role of other islet cell types. (eurospe.org)
  • Pancreatic polypeptide (PP) cells represent a minor component of the islet endocrine cell population. (eurospe.org)
  • All forms of diabetes are consequence of impaired function or survival of pancreatic islet b cells. (einsteinmed.edu)
Occur3
  • It can also occur in congenital hyperinsulinism, including nesidioblastosis. (wikipedia.org)
  • Our team is working on a study to better understand neurological problems, including seizures and developmental delays, that occur in children with hyperinsulinism, including HI/HA syndrome, and type 1 diabetes mellitus. (chop.edu)
  • An Excludes1 is used when two conditions cannot occur together, such as a congenital form versus an acquired form of the same condition. (icdlist.com)
Paternal uniparental disomy2
  • Methylation analysis, SNP-based chromosomal microarray and short tandem repeat markers analysis revealed mosaic segmental paternal uniparental disomy (UPD) 11p15.5-p15.1 in the pancreatic tissue, but not the peripheral blood, suggestive of BWS/BW-spectrum HI. (biomedcentral.com)
  • Herein, we report a case of a large-for-gestational-age infant with medically refractory HI due to a paternally transmitted K ATP mutation, who was subsequently diagnosed with mosaic BWS related to mosaic segmental pUPD (paternal uniparental disomy) 11 based on molecular testing of the pancreatic lesion. (biomedcentral.com)
Adults3
  • The Pancreatic Disorders Program provides individualized care to children and young adults with pancreatic disease. (chop.edu)
  • A non-profit dedicated to improving the lives of children, adults, and families living with congenital hyperinsulinism. (jscreen.org)
  • We are doing this study to see if the patterns of abnormalities in controlling insulin in children and adults with hyperinsulinism are related to any underlying genetic cause and to identify possible new genetic causes. (chop.edu)
Disorder2
  • Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder due to enzyme defects in adrenal steroidogenesis. (bvsalud.org)
  • Hyperinsulinism is a congenital disorder of regulation of insulin secretion. (chop.edu)
Transient1
Glucagon1
Concomitant1
  • In a cohort of children with HI and BWS, it was demonstrated that most did not have a concomitant K ATP defect, however they did have pancreatic lesions significantly larger than those seen in cases of focal HI [ 5 ]. (biomedcentral.com)
Spontaneous1
  • That spontaneous hyperinsulinism might be a cause of symptomatic hypoglycemia was first proposed by Seale Harris , MD, 1924, in Journal of the American Medical Association . (ipfs.io)
Pediatric1
  • US FDA has granted priority review designation to dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism (CHI) for up to 3 weeks of dosing with a Prescription Drug User Fee Act (PDUFA) date on December 30, 2023. (biotech-365.com)
PUPD2
  • A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. (lu.se)
  • In addition, this is the first report that demonstrated the level of paternal inherited c.1792 T pathogenic variant in the pancreatic tissue being directly correlated to the mosaic level of pUPD. (biomedcentral.com)
Disorders1
  • Your child's care team isn't just comprised of experts in delivering treatment - our specialists are actively involved in research to develop new, innovative ways to treat pancreatic disorders more safely and effectively. (chop.edu)
Children3
Diazoxide2
KCNJ111
  • Pancreatic Histopathology of Human Monogenic Diabetes Due to Causal Variants in KCNJ11, HNF1A, GATA6, and LMNA. (uchicago.edu)
Ovarian1
Medically1
Treatments2
  • Karen's research focuses on understanding pancreatic beta-cell development and function in order to develop new treatments for diseases including diabetes and congenital hyperinsulinism. (manchester.ac.uk)
  • The principal treatments of hyperinsulinism due to insulin resistance are measures that improve insulin sensitivity, such as weight loss, physical exercise, and drugs such as thiazolidinediones or metformin . (ipfs.io)
Diseases2
Severity1
  • It is characterized by dysregulated insulin secretion from pancreatic β-cells and is a group of heterogeneous conditions that vary in terms of clinical severity, histopathology and molecular aetiology. (biomedcentral.com)
Individuals2
  • Pancreatic cancer Trans fats Often, individuals get metabolically (internally) sick before showing signs of obesity. (wikipedia.org)
  • A molecular exploration of human pancreata could also help identify biomarkers highly specific for T1D, develop means of controlling the regenerative capacity of the pancreatic compartment in individuals with T1D, and design therapeutic strategies to delay or stop the progression towards full-blown T1D by slowing or preventing the development of beta cell-specific autoimmunity. (nih.gov)
Symptoms1
Tissue2
  • 70% of the pancreatic tissue and a small pancreatoblastoma. (lu.se)
  • Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. (lu.se)
Types1
Gene3
Treatment3
  • The purpose of this study is to look at the safety and tolerability (how well you will react) of the study drug (HM15136) and to determine if it is effective for the treatment of Congenital Hyperinsulinism (HI). (chop.edu)
  • The Northern Congenital Hyperinsulinism (NORCHI) service is a highly specialised service for the treatment of the rare disease of Congenital Hyperinsulinism (CHI) in the North of the UK. (norchi.nhs.uk)
  • NORCHI provides a comprehensive range of investigations and treatment options including 18-Fluoro-Dopa PET-CT scanning and pancreatic surgery to help patients and families manage this condition in the best possible way. (norchi.nhs.uk)
Molecular1
Typically1
  • Even then, about half continue to have hypoglycemia," she noted, adding that diabetes and pancreatic insufficiency then typically develop after about a decade. (medscape.com)
Excessive insulin1
Blood3
  • Poorly controlled blood sugar in women who have diabetes during pregnancy has also been linked to a high rate of congenital heart defects. (pharmaceuticalintelligence.com)
  • Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. (ipfs.io)
  • In addition to being a risk factor for type 2 diabetes , hyperinsulinism due to insulin resistance may increase blood pressure and contribute to hypertension by direct action on vascular endothelial cells (the cells lining blood vessels). (ipfs.io)
Defects1