{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:45Z","timestamp":1784557065042,"version":"3.55.0"},"reference-count":18,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,16]]},"abstract":"Summary<\/jats:title>\n \n Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resulting in severe hyperglycaemia is extremely uncommon and not reported previously in the context of HH due to\n HNF4A<\/jats:italic>\n mutation. We report a novel observation of exceptional diazoxide sensitivity in a patient with HH due to\n HNF4A<\/jats:italic>\n mutation. A female infant presented with severe persistent neonatal hypoglycaemia and was diagnosed with HH. Standard doses of diazoxide (5\u2009mg\/kg\/day) resulted in marked hyperglycaemia (maximum blood glucose 21.6\u2009mmol\/L) necessitating discontinuation of diazoxide. Lower dose of diazoxide (1.5\u2009mg\/kg\/day) successfully controlled HH in the proband, which was subsequently confirmed to be due to a novel\n HNF4A<\/jats:italic>\n mutation. At 3 years of age, the patient maintains age appropriate fasting tolerance on low dose diazoxide (1.8\u2009mg\/kg\/day) and has normal development. Diagnosis in proband\u2019s mother and maternal aunt, both of whom carried\n HNF4A<\/jats:italic>\n mutation and had been diagnosed with presumed type 1 and type 2 diabetes mellitus, respectively, was revised to maturity-onset diabetes of young (MODY). Proband\u2019s 5-year-old maternal cousin, also carrier of\n HNF4A<\/jats:italic>\n mutation, had transient neonatal hypoglycaemia. To conclude, patients with HH due to\n HNF4A<\/jats:italic>\n mutation may require lower diazoxide than other group of patients with HH. Educating the families about the risk of marked hyperglycaemia with diazoxide is essential. The clinical phenotype of\n HNF4A<\/jats:italic>\n mutation can be extremely variable.\n <\/jats:p>\n \n Learning points:<\/jats:title>\n \n \n Awareness of risk of severe hyperglycaemia with diazoxide is important and patients\/families should be accordingly educated.<\/jats:p>\n <\/jats:list-item>\n \n \n Some patients with HH due to\n HNF4A<\/jats:italic>\n mutations may require lower than standard doses of diazoxide.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The clinical phenotype of\n HNF4A<\/jats:italic>\n mutation can be extremely variable.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-19-0013","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T11:33:48Z","timestamp":1558006428000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":5,"title":["Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation"],"prefix":"10.1530","volume":"2019","author":[{"given":"Ved Bhushan","family":"Arya","sequence":"first","affiliation":[{"name":"1Department of Paediatric Endocrinology, Variety Club Children\u2019s Hospital, King\u2019s College Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kalitsi","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Variety Club Children\u2019s Hospital, King\u2019s College Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hickey","sequence":"additional","affiliation":[{"name":"2Department of Neonatology, King\u2019s College Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"3Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika R","family":"Kapoor","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Variety Club Children\u2019s Hospital, King\u2019s College Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref111","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.2337\/db07-1657","article-title":"Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4. 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