title: Congenital hyperinsulinism: clinical and molecular analysis of a large Italian cohort.
abstract: Congenital hyperinsulinism (CHI) is a genetic disorder characterized by profound hypoglycemia related to an inappropriate insulin secretion. It is a heterogeneous disease classified into two major subgroups: "channelopathies" due to defects in ATP-sensitive potassium channel, encoded by ABCC8 and KCNJ11 genes, and "metabolopathies" caused by mutation of several genes (GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) and involved in different metabolic pathways. To elucidate the genetic etiology of CHI in the Italian population, we conducted an extensive sequencing analysis of the CHI-related genes in a large cohort of 36 patients: Twenty-nine suffering from classic hyperinsulinism (HI) and seven from hyperinsulinism-hyperammonemia (HI/HA). Seventeen mutations have been found in fifteen HI patients and five mutations in five HI/HA patients. Our data confirm the major role of ATP-sensitive potassium channel in the pathogenesis of Italian cases (~70%) while the remaining percentage should be attributed to other. A better knowledge of molecular basis of CHI would lead to improve strategies for genetic screening and prenatal diagnosis. Moreover, genetic analysis might also help to distinguish the two histopathological forms of CHI, which would lead to a clear improvement in the treatment and in genetic counseling.
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy. faletra@burlo.trieste.it
authors.forename: Flavio
authors.initials: F
authors.lastname: Faletra
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Athanasakis
authors.forename: Anna
authors.initials: A
authors.lastname: Morgan
authors.forename: Xevi
authors.initials: X
authors.lastname: Biarnés
authors.forename: Federico
authors.initials: F
authors.lastname: Fornasier
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Francesca
authors.initials: F
authors.lastname: Furlan
authors.forename: Arianna
authors.initials: A
authors.lastname: Boiani
authors.forename: Arianna
authors.initials: A
authors.lastname: Maiorana
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: Laura
authors.initials: L
authors.lastname: Giordano
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D015331:Cohort Studies; D003198:Computer Simulation; D044903:Congenital Hyperinsulinism / Q000235:genetics*; D005260:Female; D000081410:Germinal Center Kinases; D005969:Glutamate Dehydrogenase / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D022124:Hyperammonemia / Q000235:genetics; D007223:Infant; D007558:Italy; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D037761:Sirtuins / Q000235:genetics; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000081410:Germinal Center Kinases; D005969:Glutamate Dehydrogenase; D051557:Hepatocyte Nuclear Factor 4; D024101:Mitochondrial Proteins; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011955:Receptors, Drug; D037761:Sirtuins; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C496592:HNF4A protein, human; C561840:GLUD1 protein, human; C525357:SIRT4 protein, human