{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T20:15:05Z","timestamp":1787948105931,"version":"build-2784847793"},"reference-count":26,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"Summary<\/jats:title>\n \n background: Congenital hyperinsulinism (CHI) is a rare genetic disorder characterised by inappropriate insulin secretion in the face of severe hypoglycaemia. There are two histological subtypes of CHI namely diffuse and focal. Diffuse CHI is most common due to recessive mutations in\n ABCC8\/KCNJ11<\/jats:italic>\n (which encode the SUR\/KIR6.2 components of the pancreatic \u03b2-cell K\n ATP<\/jats:sub>\n channel) whereas focal CHI is due to a paternally inherited\n ABCC8\/KCNJ11<\/jats:italic>\n mutation and somatic loss of heterozygosity for the 11p allele inside the focal lesion. Fluorine-18-\n l<\/jats:sc>\n -dihydroxyphenylalanine positron emission tomography\/computed tomography (\n 18<\/jats:sup>\n F-DOPA-PET\/CT) is used in the pre-operative localisation of focal lesions prior to surgery. Diffuse CHI if medically unresponsive will require a near total pancreatectomy whereas focal CHI will only require a limited lesionectomy, thus curing the patient from the hypoglycaemia.\n <\/jats:p>\n \n Aims: To report the first case of genetically confirmed CHI in Singapore from a heterozygous paternally inherited\n ABCC8<\/jats:italic>\n mutation.\n <\/jats:p>\n \n Methods\/Results: A term male infant presented with severe hyperinsulinaemic hypoglycaemia (HH) after birth and failed medical treatment with diazoxide and octreotide. Genetic testing (paternally inherited mutation in\n ABCC8<\/jats:italic>\n \/p.D1472N) suggested focal disease, but due to the unavailability of\n 18<\/jats:sup>\n F-DOPA-PET\/CT to confirm focal disease, a partial pancreatectomy was performed. Interestingly, histology of the resected pancreatic tissue showed changes typical of diffuse disease.\n <\/jats:p>\n \n Conclusion: Heterozygous paternally inherited\n ABCC8\/KCNJ11<\/jats:italic>\n mutations can lead to diffuse or focal CHI.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n HH is a cause of severe hypoglycaemia in the newborn period.<\/jats:p>\n <\/jats:list-item>\n \n \n Paternal mutations in\n ABCC8\/KCNJ11<\/jats:italic>\n can lead to diffuse or focal disease.\n <\/jats:p>\n <\/jats:list-item>\n \n \n 18<\/jats:sup>\n F-DOPA-PET\/CT scan is the current imaging of choice for localising focal lesions.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Gallium-68 tetra-aza-cyclododecane-\n N<\/jats:italic>\n N<\/jats:italic>\n \u2032\n N<\/jats:italic>\n \u2033\n N<\/jats:italic>\n -\u2034-tetra-acetate octreotate PET scan is not a useful imaging tool for localising focal lesions.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The molecular mechanism by which a heterozygous\n ABCC8<\/jats:italic>\n mutation leads to diffuse disease is currently unclear.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Focal lesions are curable by lesionectomy and so genetic studies in patients with HH must be followed by imaging using\n 18<\/jats:sup>\n F-DOPA-PET\/CT scan.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/edm-13-0041","type":"journal-article","created":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T05:59:55Z","timestamp":1383890395000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":5,"title":["Paternally inherited ABCC8 mutation causing diffuse congenital hyperinsulinism"],"prefix":"10.1530","volume":"2013","author":[{"given":"Suresh","family":"Chandran","sequence":"first","affiliation":[{"name":"1Departments of Neonatology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Yap Kok Peng","sequence":"additional","affiliation":[{"name":"2Paediatric Endocrinology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Samuel","family":"Rajadurai","sequence":"additional","affiliation":[{"name":"1Departments of Neonatology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap","family":"Te Lu","sequence":"additional","affiliation":[{"name":"3Paediatric Surgery, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth T E","family":"Chang","sequence":"additional","affiliation":[{"name":"4Children's Pathology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"5Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ellard","sequence":"additional","affiliation":[{"name":"5Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Hussain","sequence":"additional","affiliation":[{"name":"6Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref121","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jpeds.2005.11.015","article-title":"Neonatal hypoglycemia and occipital 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