{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:58:09Z","timestamp":1771934289911,"version":"3.50.1"},"reference-count":17,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223187\/Z\/21\/Z"],"award-info":[{"award-number":["223187\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Care Research Exeter Biomedical Research Centre"},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hyperinsulinemic hypoglycemia (HI) is a rare feature in individuals with coloboma, heart defects, atresia choanae, retardation of growth and development, genital abnormalities, and ear abnormalities (CHARGE) syndrome, though its underlying mechanisms remain poorly understood. We report a Chilean female proband with genetically confirmed CHARGE syndrome caused by a pathogenic variant in the CHD7 gene, who presented with HI in the neonatal period. Initial hypoglycemia was detected on days 2-3 of life, followed by recurrent episodes prompting biochemical investigation. On day 21, HI was biochemically confirmed. Comprehensive hormonal evaluation, including cortisol and growth hormone testing, excluded deficiencies in these hormones as contributing factors. Genetic screening of 22 known HI-associated genes revealed no pathogenic variants, supporting the hypothesis that HI in this case is related to CHARGE syndrome rather than being a coincidental finding. The patient responded well to diazoxide treatment, which allowed for maintenance of normoglycemia, with gradual dose reduction as glucose management normalized. This case, along with 2 previously reported cases, suggests that HI can be an integral part of CHARGE syndrome. Further research is needed to understand the mechanisms connecting CHD7 variants and HI and to refine management strategies for affected individuals.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag016","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:13:01Z","timestamp":1769515981000},"source":"Crossref","is-referenced-by-count":0,"title":["Congenital hyperinsulinism in an individual with CHARGE syndrome and a pathogenic\n                    <i>CHD7<\/i>\n                    variant"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7690-6082","authenticated-orcid":false,"given":"Consuelo","family":"Ibeas","sequence":"first","affiliation":[{"name":"Institute of Maternal and Child Research, University of Chile , Santiago 8360160 ,","place":["Chile"]},{"name":"Pediatrics Department, Clinical Hospital San Borja Arriar\u00e1n , Santiago 8360160 ,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-1219","authenticated-orcid":false,"given":"Franco","family":"Giraudo","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, University of Chile , Santiago 8360160 ,","place":["Chile"]},{"name":"Pediatrics Department, Clinical Hospital San Borja Arriar\u00e1n , Santiago 8360160 ,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0596-0719","authenticated-orcid":false,"given":"Jonna M E","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Science, University of Exeter , Exeter EX2 5DW ,","place":["UK"]},{"name":"Kuopio Pediatric Research Unit (KuPRu), University of Eastern Finland , Kuopio FI-70211 ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-6340","authenticated-orcid":false,"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Science, University of Exeter , Exeter EX2 5DW ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-0181","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Mericq","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, University of Chile , Santiago 8360160 ,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"issue":"4","key":"2026022405593915800_luag016-B1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/jmg.2005.036061","article-title":"CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene","volume":"43","author":"Jongmans","year":"2006","journal-title":"J Med Genet"},{"issue":"1","key":"2026022405593915800_luag016-B2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13052-022-01341-3","article-title":"CHARGE syndrome presenting with persistent hypoglycemia: case report and overview of the main genetic syndromes associated with neonatal hypoglycemia","volume":"48","author":"Consales","year":"2022","journal-title":"Ital J Pediatr"},{"issue":"4","key":"2026022405593915800_luag016-B3","first-page":"487","article-title":"Neonatal presentation of growth hormone deficiency in CHARGE syndrome: the benefit of early treatment on long-term growth","volume":"64","author":"Costa","year":"2020","journal-title":"Arch Endocrinol Metab"},{"issue":"6","key":"2026022405593915800_luag016-B4","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ejmg.2018.01.008","article-title":"A case of CHARGE syndrome associated with hyperinsulinemic hypoglycemia in infancy","volume":"61","author":"Sekiguchi","year":"2018","journal-title":"Eur J Med Genet"},{"issue":"4","key":"2026022405593915800_luag016-B5","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/ajmg.c.31586","article-title":"Gastrointestinal and feeding difficulties in CHARGE syndrome: a review from head-to-toe","volume":"175","author":"Blake","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"3","key":"2026022405593915800_luag016-B6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000531766","article-title":"International guidelines for the diagnosis and management of hyperinsulinism","volume":"97","author":"De Leon","year":"2024","journal-title":"Horm Res Paediatr"},{"issue":"2","key":"2026022405593915800_luag016-B7","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/ajmg.a.37435","article-title":"Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria","volume":"170","author":"Hale","year":"2016","journal-title":"Am J Med Genet A"},{"issue":"9","key":"2026022405593915800_luag016-B8","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1007\/s00125-013-2962-5","article-title":"Improved genetic testing for monogenic diabetes using targeted next-generation sequencing","volume":"56","author":"Ellard","year":"2013","journal-title":"Diabetologia"},{"issue":"3","key":"2026022405593915800_luag016-B9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/cen.14393","article-title":"Syndromic forms of hyperinsulinaemic hypoglycaemia\u2014a 15-year follow-up study","volume":"94","author":"Kostopoulou","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"2026022405593915800_luag016-B10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/pedi.13333","article-title":"Increased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non-genetic risk factors in this group","volume":"23","author":"Hewat","year":"2022","journal-title":"Pediatr Diabetes"},{"issue":"6","key":"2026022405593915800_luag016-B11","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.jpeds.2015.02.045","article-title":"Re-evaluating \u201ctransitional neonatal hypoglycemia\u201d: mechanism and implications for management","volume":"166","author":"Stanley","year":"2015","journal-title":"J Pediatr"},{"issue":"8","key":"2026022405593915800_luag016-B12","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1210\/jc.2003-030137","article-title":"Spontaneous hypoglycemia in childhood is accompanied by paradoxically low Serum growth hormone and appropriate cortisol counterregulatory hormonal responses","volume":"88","author":"Hussain","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2026022405593915800_luag016-B13","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1210\/jc.2003-030135","article-title":"Neonates with symptomatic hyperinsulinemic hypoglycemia generate inappropriately low Serum cortisol counterregulatory hormonal responses","volume":"88","author":"Hussain","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2026022405593915800_luag016-B14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3803\/EnM.2019.34.2.187","article-title":"Impaired cortisol and growth hormone counterregulatory responses among severe hypoglycemic patients with type 2 diabetes Mellitus","volume":"34","author":"Rhyu","year":"2019","journal-title":"Endocrinology and Metabolism"},{"issue":"4","key":"2026022405593915800_luag016-B15","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1530\/EJE-12-0673","article-title":"Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism","volume":"168","author":"Kapoor","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"2026022405593915800_luag016-B16","doi-asserted-by":"crossref","first-page":"1013874","DOI":"10.3389\/fendo.2023.1013874","article-title":"Syndromic forms of congenital hyperinsulinism","volume":"14","author":"Zenker","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2026022405593915800_luag016-B17","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13023-016-0547-3","article-title":"Conservatively treated congenital hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time","volume":"11","author":"Salomon-Estebanez","year":"2016","journal-title":"Orphanet J Rare Dis"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/3\/luag016\/67089693\/luag016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/3\/luag016\/67089693\/luag016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:59:47Z","timestamp":1771930787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag016\/8495840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,23]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2,23]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag016","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,23]]},"article-number":"luag016"}}