{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:02:15Z","timestamp":1792512135877,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n<jats:title>Context<\/jats:title>\n<jats:p>Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic \u03b2-cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To characterize clinically and genetically CHI patients in Spain.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design and methods<\/jats:title>\n<jats:p>We included 50 patients with CHI from Spain. Clinical information was provided by the referring clinicians. Mutational analysis was carried out for <jats:italic>KCNJ11<\/jats:italic>, <jats:italic>ABCC8<\/jats:italic>, and<jats:italic> GCK<\/jats:italic> genes. The <jats:italic>GLUD1<\/jats:italic>, <jats:italic>HNF4A<\/jats:italic>, <jats:italic>HNF1A<\/jats:italic>, <jats:italic>UCP2<\/jats:italic>, and <jats:italic>HADH<\/jats:italic> genes were sequenced depending on the clinical phenotype.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>We identified the genetic etiology in 28 of the 50 CHI patients tested: 21 had a mutation in K<jats:sub>ATP<\/jats:sub> channel genes (42%), three in <jats:italic>GLUD1<\/jats:italic> (6%), and four in <jats:italic>GCK<\/jats:italic> (8%). Most mutations were found in <jats:italic>ABCC8<\/jats:italic> (20\/50). Half of these patients (10\/20) were homozygous or compound heterozygous, with nine being unresponsive to diazoxide treatment. The other half had heterozygous mutations in <jats:italic>ABCC8<\/jats:italic>, six of them being unresponsive to diazoxide treatment and four being responsive to diazoxide treatment. We identified 22 different mutations in the K<jats:sub>ATP<\/jats:sub> channel genes, of which ten were novel. Notably, patients with <jats:italic>ABCC8<\/jats:italic> mutations were diagnosed earlier, with lower blood glucose levels and required higher doses of diazoxide than those without a genetic diagnosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Genetic analysis revealed mutations in 56% of the CHI patients. <jats:italic>ABCC8<\/jats:italic> mutations are the most frequent cause of CHI in Spain. We found ten novel mutations in the K<jats:sub>ATP<\/jats:sub> channel genes. The genetic diagnosis is more likely to be achieved in patients with onset within the first week of life and in those who fail to respond to diazoxide treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0027","type":"journal-article","created":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T01:59:32Z","timestamp":1463536772000},"page":"717-726","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":26,"title":["Clinical and genetic characterization of congenital hyperinsulinism in Spain"],"prefix":"10.1093","volume":"174","author":[{"given":"R","family":"Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Fern\u00e1ndez-Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Velayos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Aguayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Urrutia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Rica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"_","family":"_","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"2016051718591940000_174.6.717.1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.148171"},{"key":"2016051718591940000_174.6.717.2","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0016"},{"key":"2016051718591940000_174.6.717.3","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-63"},{"key":"2016051718591940000_174.6.717.4","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0673"},{"key":"2016051718591940000_174.6.717.5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2169"},{"key":"2016051718591940000_174.6.717.6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1687-9856-2013-3","article-title":"Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management","volume":"2013","author":"Lord","year":"2013","journal-title":"International Journal of Pediatric Endocrinology"},{"key":"2016051718591940000_174.6.717.7","doi-asserted-by":"crossref","unstructured":"Pinney SE MacMullen C Becker S Lin YW Hanna C Thornton P Ganguly A Shyng SL Stanley CA. 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