{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:30:35Z","timestamp":1747193435209,"version":"3.40.5"},"reference-count":35,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Introduction:<\/i><\/b> Neonatal hypoglycemia due to congenital hyperinsulinism (CHI) is a potentially life-threatening condition. Biallelic pathogenic variants in K<sub>ATP<\/sub> channel subunit genes (<i>ABCC8<\/i>, <i>KCNJ11<\/i>), causing severe forms of CHI, are more prevalent in regions with a significant rate of consanguinity and may lead to unexplained neonatal deaths. We hypothesized that K<sub>ATP<\/sub> channel gene variants are the cause of CHI in three unrelated children from consanguineous Kurdish families with histories of four unexplained neonatal deaths with convulsions. <b><i>Cases:<\/i><\/b> (1) A girl presented on the 6th day of life with recurrent hypoglycemic convulsions (blood glucose 2.05 mmol\/L, insulin 58 mIU\/L, C-peptide 2,242 pmol\/L). (2) A girl with severe developmental delay was diagnosed with CHI at 3 years of age (blood glucose 2.78 mmol\/L, insulin 8.1 mIU\/L, C-peptide 761 pmol\/L) despite a history of recurrent hypoglycemia since neonatal age. (3) A girl presented at 3 weeks of age with convulsions and unconsciousness (blood glucose 2.5 mmol\/L, insulin 14.6 mIU\/L, C-peptide 523 pmol\/L). Coding regions of the <i>ABCC8<\/i> and <i>KCNJ11<\/i> genes were tested by Sanger sequencing. Potential variants were evaluated using the American College of Medical Genetics standards. Three novel causative homozygous variants were found \u2013 p.Trp514Ter in the <i>ABCC8<\/i> gene (Pt2), and p.Met1Val (Pt1) and p.Tyr26Ter (Pt3) in the <i>KCNJ11<\/i> gene. <b><i>Conclusion:<\/i><\/b> CHI caused by K<sub>ATP<\/sub> channel variants was elucidated in three children, providing a highly probable retrospective diagnosis for their deceased siblings. Future lives can be saved by timely diagnosis of CHI when encountering a neonate with unexplained seizures or other signs of recurrent and\/or persistent hypoglycemia.<\/jats:p>","DOI":"10.1159\/000506476","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T22:00:34Z","timestamp":1585000834000},"page":"58-65","source":"Crossref","is-referenced-by-count":3,"title":["Congenital Hyperinsulinism Caused by Novel Homozygous K<sub>ATP<\/sub> Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families"],"prefix":"10.1159","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-5824","authenticated-orcid":false,"given":"Shenali\u00a0Anne","family":"Amaratunga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Hussein\u00a0Tayeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klara","family":"Rozenkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Kucerova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-8026","authenticated-orcid":false,"given":"Stepanka","family":"Pruhova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-5375","authenticated-orcid":false,"given":"Jan","family":"Lebl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2020,3,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(05)70481-8"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-63"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30323-0"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2822"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00156"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716548"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.11.1809"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805073381904"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.1.221"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801223380404"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206605"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1159\/000351943"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040118"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1356"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1086\/520960"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016121312"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx318"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.6.1592"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003850"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23289"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12512"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2003"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3651"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2169"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1136\/fn.82.2.F98"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1989.tb00455.x"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0605"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310967"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2002.30241"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0455"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2763"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-199008000-00024"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1177\/000992288802700307"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1989.tb11198.x"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2010.753.756"}],"container-title":["Hormone 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