{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:44:28Z","timestamp":1793400268875,"version":"4.5.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.bioscientifica.com\/journals\/reuselicenceeje\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The phenotype associated with heterozygous\n                      <jats:italic>HNF4A<\/jats:italic>\n                      gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of\n                      <jats:italic>HNF4A<\/jats:italic>\n                      mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and methods<\/jats:title>\n                    <jats:p>\n                      We sequenced the\n                      <jats:italic>ABCC8<\/jats:italic>\n                      ,\n                      <jats:italic>KCNJ11<\/jats:italic>\n                      ,\n                      <jats:italic>GCK<\/jats:italic>\n                      ,\n                      <jats:italic>GLUD1<\/jats:italic>\n                      , and\/or\n                      <jats:italic>HNF4A<\/jats:italic>\n                      genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A genetic diagnosis was possible for 59\/220 (27%) patients. K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel mutations were most common (15%) followed by\n                      <jats:italic>GLUD1<\/jats:italic>\n                      mutations causing hyperinsulinism with hyperammonemia (5.9%), and\n                      <jats:italic>HNF4A<\/jats:italic>\n                      mutations (5%). Seven of the 11 probands with a heterozygous\n                      <jats:italic>HNF4A<\/jats:italic>\n                      mutation did not have a parent affected with diabetes, and four\n                      <jats:italic>de novo<\/jats:italic>\n                      mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this large series,\n                      <jats:italic>HNF4A<\/jats:italic>\n                      mutations are the third most common cause of diazoxide responsive HH. We recommend that\n                      <jats:italic>HNF4A<\/jats:italic>\n                      sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel mutations have been excluded.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-09-0861","type":"journal-article","created":{"date-parts":[[2010,2,17]],"date-time":"2010-02-17T21:11:09Z","timestamp":1266441069000},"page":"987-992","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":121,"title":["Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations"],"prefix":"10.1093","volume":"162","author":[{"given":"S E","family":"Flanagan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R R","family":"Kapoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Mali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Cody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Schwahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Siahanidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Akcay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Rubio-Cabezas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P H","family":"Shield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"6","key":"1_33873261","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1136\/adc.2008.148171","volume":"94","year":"2009","journal-title":"Archives of Disease in Childhood","ISSN":"https:\/\/id.crossref.org\/issn\/0003-9888","issn-type":"print"},{"issue":"5209","key":"2_15839122","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1126\/science.7716548","volume":"268","author":"Thomas","year":"1995","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"issue":"11","key":"3_37685794","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1093\/hmg\/5.11.1809","volume":"5","year":"1996","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"key":"4_19553937","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200363200","year":"2002","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"8","key":"5_19298077","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1172\/JCI25495","volume":"115","author":"Ashcroft","year":"2005","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"2","key":"6_18689905","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1210\/jc.2004-1604","volume":"90","year":"2005","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"19","key":"7_5977290","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1056\/NEJM199805073381904","volume":"338","author":"Stanley","year":"1998","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"5","key":"8_35417912","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1530\/EJE-09-0615","volume":"161","year":"2009","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"key":"9_37139836","first-page":"226","volume":"338","year":"1997","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"3","key":"10_11267190","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1172\/JCI200111294","volume":"108","author":"Clayton","year":"2001","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"6","key":"11_34460987","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.2337\/db08-1792","volume":"58","year":"2009","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"issue":"1","key":"12_17970930","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2337\/diabetes.53.1.221","volume":"53","author":"Molven","year":"2004","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"issue":"7","key":"13_34734820","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1210\/jc.2009-0423","volume":"94","year":"2009","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"14_29889215","doi-asserted-by":"crossref","first-page":"118e","DOI":"10.1371\/journal.pmed.0040118","volume":"4","year":"2007","journal-title":"PLOS MEDICINE"},{"key":"15_34624892","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1007\/s00125-007-0833-7","volume":"50","year":"2007","ISSN":"https:\/\/id.crossref.org\/issn\/1432-0428","issn-type":"print"},{"issue":"6","key":"16_30421999","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.2337\/db07-1657","volume":"57","year":"2008","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"issue":"9","key":"17_22517398","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/humu.20357","volume":"27","author":"Ellard","year":"2006","journal-title":"Human mutation","ISSN":"https:\/\/id.crossref.org\/issn\/1059-7794","issn-type":"print"},{"key":"18_34410136","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s00125-005-1738-y","volume":"48","year":"2005","ISSN":"https:\/\/id.crossref.org\/issn\/1432-0428","issn-type":"print"},{"issue":"1","key":"19_15971273","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1136\/adc.73.1.17","volume":"73","author":"Freeman","year":"1995","journal-title":"Archives of Disease in Childhood","ISSN":"https:\/\/id.crossref.org\/issn\/0003-9888","issn-type":"print"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/162\/5\/987.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/162\/5\/987.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T11:24:19Z","timestamp":1676373859000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/162\/5\/987\/6676620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":19,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/eje-09-0861","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5]]}}}