{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:44:27Z","timestamp":1793400267835,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>The phenotype mediated by <jats:italic>HNF4A\/HNF1A<\/jats:italic> mutations is variable and includes diazoxide-responsive hyperinsulinaemic hypoglycaemia (HH) and maturity-onset diabetes of the young (MODY).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>We characterised an international multicentre paediatric cohort of patients with <jats:italic>HNF4A<\/jats:italic>or <jats:italic>HNF1A<\/jats:italic>mutations presenting with HH over a 25-year period (1995\u20132020).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Clinical and genetic analysis data from five centres were obtained. Diazoxide responsiveness was defined as the ability to maintain normoglycaemia without intravenous glucose. Macrosomia was defined as a birth weight \u226590th centile. SPSS v.27.1 was used for data analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 34 patients (70.6% female, <jats:italic>n<\/jats:italic>\u2009\u2009= 24) with a mean age of 7.1 years (<jats:sc>s.d.<\/jats:sc> 6.4) were included. A total of 21 different heterozygous <jats:italic>HNF4A<\/jats:italic>mutations were identified in 29 patients (four novels). Four different previously described heterozygous <jats:italic>HNF1A<\/jats:italic> mutations were detected in five patients. Most (97.1%, <jats:italic>n<\/jats:italic>\u2009\u2009= 33) developed hypoglycaemia by day 2 of life. The mean birth weight was 3.8 kg (<jats:sc>s.d.<\/jats:sc> 0.8), with most infants macrosomic (<jats:italic>n<\/jats:italic>\u2009= 21, 61.8%). Diazoxide was commenced in 28 patients (82.3%); all responded. HH resolved in 20 patients (58.8%) following a median of 0.9 years (interquartile range (IQR): 0.2\u20136.8). Nine patients (<jats:italic>n<\/jats:italic>\u2009= 9, 26.5%) had developmental delay. Two patients developed Fanconi syndrome (p.Arg63Trp, <jats:italic>HNF4A<\/jats:italic>) and four had other renal or hepatic findings. Five (14.7%) developed MODY at a median of 11.0 years (IQR: 9.0\u201313.9). Of patients with inherited mutations (<jats:italic>n<\/jats:italic>\u2009= 25, 73.5%), a family history of diabetes was present in 22 (88.0%).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We build on the knowledge of the natural history and pancreatic and extra-pancreatic phenotypes of <jats:italic>HNF4A\/HNF1A<\/jats:italic>mutations and illustrate the heterogeneity of this condition.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0897","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T18:27:46Z","timestamp":1643394466000},"page":"417-427","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":18,"title":["Clinical and genetic heterogeneity of HNF4A\/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia"],"prefix":"10.1093","volume":"186","author":[{"given":"Sin\u00e9ad M","family":"McGlacken-Byrne","sequence":"first","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina Kallefullah","family":"Mohammad","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Conlon","sequence":"additional","affiliation":[{"name":"2Department of Paediatric Endocrinology, Children\u2019s Health Ireland, Temple Street, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-2869","authenticated-orcid":true,"given":"Diliara","family":"Gubaeva","sequence":"additional","affiliation":[{"name":"3Department of Paediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Siersb\u00e6k","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders J\u00f8rgen","family":"Schou","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin","family":"Demirbilek","sequence":"additional","affiliation":[{"name":"5Department of Paediatric Endocrinology, Hacettepe University, Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Dastamani","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne A L","family":"Houghton","sequence":"additional","affiliation":[{"name":"6The Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Melikyan","sequence":"additional","affiliation":[{"name":"3Department of Paediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-6853","authenticated-orcid":true,"given":"Henrik","family":"Christesen","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"7Institute of Biomedical and Clinical Science Science, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuala P","family":"Murphy","sequence":"additional","affiliation":[{"name":"2Department of Paediatric Endocrinology, Children\u2019s Health Ireland, Temple Street, Dublin, Ireland"},{"name":"8School of Medicine, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-8297","authenticated-orcid":true,"given":"Pratik","family":"Shah","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"},{"name":"9Department of Paediatric Endocrinology, The Royal London Children's Hospital, Barts Health NHS Trust, London, UK"},{"name":"10Centre of Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/186\/4\/EJE-21-0897.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/186\/4\/EJE-21-0897.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:17:17Z","timestamp":1676391437000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/186\/4\/417\/6852977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,1]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0897","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,1]]}}}