{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:43:10Z","timestamp":1790206990658,"version":"4.1.0"},"reference-count":24,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/deed.en_GB"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,11]]},"abstract":"Summary<\/jats:title>\n \n We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous\n ABCC8<\/jats:italic>\n mutation. A term baby, with birth weight 3.8\u2009kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15\u2009mg\/kg\/min), but despite escalation to a maximum dose (15\u2009mg\/kg\/day), intravenous (i.v.) glucose requirement remained high (13\u2009mg\/kg\/min). Genetic testing demonstrated a homozygous\n ABCC8<\/jats:italic>\n splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10\u2009mg\/kg\/day of diazoxide and 40\u2009\u00b5g\/kg\/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous\n ABCC8<\/jats:italic>\n mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited\n ABCC8<\/jats:italic>\n mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity.\n <\/jats:p>\n \n Learning points:<\/jats:title>\n \n \n \n Homozygous\n ABCC8<\/jats:italic>\n mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia.\n <\/jats:p>\n <\/jats:list-item>\n \n \n This case highlights that partial diazoxide responsiveness in homozygous\n ABCC8<\/jats:italic>\n mutations may be present.\n <\/jats:p>\n <\/jats:list-item>\n \n Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guemes","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"},{"name":"3Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK"}],"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":"Clare","family":"Gilbert","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"4Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[{"name":"4Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Barton","sequence":"additional","affiliation":[{"name":"5Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Dattani","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"},{"name":"3Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratik","family":"Shah","sequence":"additional","affiliation":[{"name":"1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, UK"},{"name":"3Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref211","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1365-2265.2011.04203.x","article-title":"Congenital hyperinsulinism: marked clinical heterogeneity in siblings with identical mutations in the ABCC8 gene","volume":"76","year":"2012","journal-title":"Clinical Endocrinology"},{"key":"ref101","first-page":"287","article-title":"Congenital hyperinsulinism due to a compound heterozygous ABCC8 mutation with spontaneous resolution at eight 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