{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:05:13Z","timestamp":1789207513438,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,12]],"date-time":"2013-12-12T00:00:00Z","timestamp":1386806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocyte nuclear factor\u00a04 alpha (<jats:italic><jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>4A<\/jats:italic>) gene mutations have a well\u2010recognized role in maturity\u2010onset diabetes of the young and have recently been described in congenital hyperinsulinism. A biphasic phenotype has been postulated, with macrosomia and congenital hyperinsulinism in infancy, and diabetes in young adulthood. In this case series, we report three children with <jats:italic><jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>4A<\/jats:italic> mutations (two de novo) and diazoxide\u2010responsive congenital hyperinsulinism, highlighting the potential for ongoing diazoxide requirement and the importance of screening for these mutations even in the absence of family history.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case reports<\/jats:title><jats:p>All patients presented with macrosomia (mean birthweight 4.26\u00a0kg) and hyperinsulinaemic hypoglycaemia soon after birth (median age 1\u00a0day). All three (age range 7\u00a0months to 11\u00a0years 10\u00a0months) remain on diazoxide therapy, with dose requirements increasing in one patient. There was no prior family history of diabetes, neonatal hypoglycaemia or macrosomia. Parents were screened for <jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>4A mutations post\u2010diagnosis and one father was subsequently found to have maturity\u2010onset diabetes of the young.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This case series follows the evolving course of three patients with confirmed <jats:italic><jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>4A<\/jats:italic>\u2010mediated congenital hyperinsulinism, highlighting (1) the variable natural history of these mutations, (2) the potential for prolonged diazoxide requirement, even into adolescence, and (3) the need for screening, regardless of family history.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12259","type":"journal-article","created":{"date-parts":[[2013,6,24]],"date-time":"2013-06-24T14:59:59Z","timestamp":1372085999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The evolving course of <i><scp>HNF<\/scp>4A<\/i> hyperinsulinaemic hypoglycaemia\u2014a case series"],"prefix":"10.1111","volume":"31","author":[{"given":"S. M.","family":"McGlacken\u2010Byrne","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Hawkes","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ellard","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0368"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.064337"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.148171"},{"key":"e_1_2_5_5_1","first-page":"3026","article-title":"Congenital hyperinsulinism\u2014new causes and clinical variations","volume":"173","author":"Bruun MF","year":"2011","journal-title":"Ugeskr Laeger"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-1136"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2010.10.004"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1657"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2011.04.002"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040118"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0861"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1356"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0833-7"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20357"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302546"},{"key":"e_1_2_5_16_1","first-page":"33","article-title":"Development of the pancreas and neonatal diabetes","volume":"12","author":"Shield J","year":"2007","journal-title":"Endocr Dev"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522365"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507496200"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241349398"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/384458a0"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.6.699"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12259","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:05:09Z","timestamp":1696377909000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,12]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1111\/dme.12259"],"URL":"https:\/\/doi.org\/10.1111\/dme.12259","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,12]]},"assertion":[{"value":"2013-06-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}