{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T21:52:23Z","timestamp":1769032343254,"version":"3.49.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["320030-152938"],"award-info":[{"award-number":["320030-152938"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Desir\u00e9e and Niels Yde Foundation","award":["389-12"],"award-info":[{"award-number":["389-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The most common cause of endogenous hyperinsulinemic hypoglycemia in neonates [congenital hyperinsulinemic hypoglycemia (CHH)] is different monogenic forms of gene mutations. About 50% of the mutations are known. We present a new mutation within the short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADH) gene causing CHH in 2 related patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The course of 2 consanguineous patients with CHH are presented with a follow-up of &amp;gt;30 years. NextSeq 500 sequencing was performed and confined on known genes with autosomal recessive inheritance, namely ABCC8 (MANE Select: NM_00352.6), HADH (MANE Select: NM_005327.7), and KCNJ11 (MANE Select: NM_00525.4). Acylcarnitine profiles were measured and 68Ga-DOTA exendin positron emission tomography\/computer tomography was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CHH was diagnosed in both patients in the neonatal period. A therapy with diazoxid was initiated, which initially stabilized the disease in both children. With advancing age, more hypoglycemic events occurred with an increase in carbohydrate intake, leading to obesity in both patients. In addition to diazoxide, somatostatin analogues were successfully added in adulthood. A genetic analysis documented a new homozygote mutation in the HADH gene (HADH-variant c.796G &amp;gt; T). An acylcarnitine profile showed an increased plasma butyryl-carnitine, consistent with a dysfunction of the HADH enzyme. 68Gallium-DOTA-exendin showed an increased uptake in the whole pancreas in both patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Clinical presentation, biochemical workup, and therapeutical response to diazoxide and somatostatin analogues are consistent with previous reports of HADH mutations. The overexpression of glucagon-like peptide 1 receptors in this context warrants further research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf423","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T11:46:11Z","timestamp":1753357571000},"page":"358-365","source":"Crossref","is-referenced-by-count":0,"title":["Congenital Hyperinsulinemic Hypoglycemia With a New HADH Mutation and Pancreatic Overexpression of GLP-1 Receptors"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3985-3379","authenticated-orcid":false,"given":"Andrea","family":"Widmer","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urs","family":"Zumsteg","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, University Children's Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-2597","authenticated-orcid":false,"given":"Gabor","family":"Szinnai","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, University Children's Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Filges","sequence":"additional","affiliation":[{"name":"Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Meier","sequence":"additional","affiliation":[{"name":"Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"De Geyter","sequence":"additional","affiliation":[{"name":"Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwadwo","family":"Antwi","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-5350","authenticated-orcid":false,"given":"Damian","family":"Wild","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Marc","family":"Nuoffer","sequence":"additional","affiliation":[{"name":"Division of Laboratory Medicine, University Hospital Berne, Inselspital , Bern CH-3010 ,","place":["Switzerland"]},{"name":"University Children's Hospital, University Hospital Bern, Inselspital , Bern CH-3010 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-4606","authenticated-orcid":false,"given":"Emanuel","family":"Christ","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel , Basel CH-4031 ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"issue":"3","key":"2026012101525446300_dgaf423-B1","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1210\/jc.2015-3651","article-title":"Perspective on the genetics and diagnosis of congenital hyperinsulinism disorders","volume":"101","author":"Stanley","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026012101525446300_dgaf423-B2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1053\/j.sempedsurg.2010.10.012","article-title":"KATP channel mutations in congenital hyperinsulinism","volume":"20","author":"Saint-Martin","year":"2011","journal-title":"Semin Pediatr Surg"},{"key":"2026012101525446300_dgaf423-B3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fendo.2019.00111","article-title":"The genetic and molecular mechanisms of congenital hyperinsulinism","volume":"10","author":"Galcheva","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026012101525446300_dgaf423-B4","doi-asserted-by":"crossref","first-page":"101351","DOI":"10.1016\/j.molmet.2021.101351","article-title":"GLP-1 physiology informs the pharmacotherapy of obesity","volume":"57","author":"Drucker","year":"2022","journal-title":"Mol Metab"},{"issue":"5","key":"2026012101525446300_dgaf423-B5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00259-003-1184-3","article-title":"Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting","volume":"30","author":"Reubi","year":"2003","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"2","key":"2026012101525446300_dgaf423-B6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S2213-8587(13)70049-4","article-title":"Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study","volume":"1","author":"Christ","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026012101525446300_dgaf423-B7","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1007\/s00259-018-4101-5","article-title":"Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET\/CT, SPECT\/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study","volume":"45","author":"Antwi","year":"2018","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2026012101525446300_dgaf423-B8","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1530\/ERC-19-0476","article-title":"Innovative imaging of insulinoma: the end of sampling? A review","volume":"27","author":"Christ","year":"2020","journal-title":"Endocr Relat Cancer"},{"issue":"5","key":"2026012101525446300_dgaf423-B9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"2026012101525446300_dgaf423-B10","doi-asserted-by":"publisher","author":"Ellard","DOI":"10.1101\/531210"},{"issue":"11","key":"2026012101525446300_dgaf423-B11","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum Mutat"},{"issue":"1","key":"2026012101525446300_dgaf423-B12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1186\/s13023-021-02088-6","article-title":"Genetic pathogenesis, diagnosis, and treatment of short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism","volume":"16","author":"Zhang","year":"2021","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"2026012101525446300_dgaf423-B13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1172\/JCI200111294","article-title":"Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of \u03b2-oxidation in insulin secretion","volume":"108","author":"Clayton","year":"2001","journal-title":"J Clin Invest"},{"key":"2026012101525446300_dgaf423-B14","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1210\/clinem\/dgae459","article-title":"Clinical and genetic characteristics of congenital hyperinsulinism in Norway: a nationwide cohort study","volume":"110","author":"Velde","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026012101525446300_dgaf423-B15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bbrc.2007.10.188","article-title":"Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency","volume":"368","author":"Filling","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"issue":"41","key":"2026012101525446300_dgaf423-B16","doi-asserted-by":"crossref","first-page":"31806","DOI":"10.1074\/jbc.M110.123638","article-title":"Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase","volume":"285","author":"Li","year":"2010","journal-title":"J Biol Chem"},{"key":"2026012101525446300_dgaf423-B17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-030-02961-6_3","volume-title":"Congenital Hyperinsulinism: A Practical Guide to Diagnosis and Management","author":"Rayannavar","year":"2019"},{"issue":"2","key":"2026012101525446300_dgaf423-B18","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4274\/jcrpe.1963","article-title":"A deep intronic HADH splicing mutation (c.636 + 471G &gt; T) in a congenital hyperinsulinemic hypoglycemia case: long term clinical course","volume":"7","author":"\u00c7amtosun","year":"2015","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"2","key":"2026012101525446300_dgaf423-B19","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1159\/000485184","article-title":"A multicenter experience with long-acting somatostatin analogues in patients with congenital hyperinsulinism","volume":"89","author":"Van Der Steen","year":"2018","journal-title":"Horm Res Paediatr"},{"key":"2026012101525446300_dgaf423-B20","first-page":"188","article-title":"18F-FDOPA and 68 ga-dotatate PET imaging in congenital hyperinsulinism","volume":"11","author":"Djekidel","year":"2021","journal-title":"Am J Nucl Med Mol Imaging"},{"issue":"2","key":"2026012101525446300_dgaf423-B21","doi-asserted-by":"crossref","first-page":"310","DOI":"10.2967\/jnumed.121.262327","article-title":"68Ga-NODAGA-Exendin-4 PET\/CT improves the detection of focal congenital hyperinsulinism","volume":"63","author":"Boss","year":"2022","journal-title":"J Nucl Med"},{"key":"2026012101525446300_dgaf423-B22","doi-asserted-by":"crossref","first-page":"132256","DOI":"10.1016\/j.ijbiomac.2024.132256","article-title":"Achyranthes bidentata polysaccharide ameliorates type 2 diabetes mellitus by gut microbiota-derived short-chain fatty acids-induced activation of the GLP-1\/GLP-1R\/cAMP\/PKA\/CREB\/INS pathway","volume":"270","author":"Xia","year":"2024","journal-title":"Int J Biol Macromol"},{"issue":"4","key":"2026012101525446300_dgaf423-B23","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.bbrc.2015.02.139","article-title":"Protection of pancreatic \u03b2-cells against glucotoxicity by short-term treatment with GLP-1","volume":"459","author":"Park","year":"2015","journal-title":"Biochem Biophys Res Commun"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf423\/63842354\/dgaf423.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/2\/358\/63842354\/dgaf423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/2\/358\/63842354\/dgaf423.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:53:22Z","timestamp":1768978402000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/111\/2\/358\/8211966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,7,25]]},"published-print":{"date-parts":[[2026,1,21]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf423","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2025,7,25]]}}}