Congenital Hyperinsulinism Caused by Novel Homozygous K<sub>ATP</sub> Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families

<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 – 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.

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TitleCongenital Hyperinsulinism Caused by Novel Homozygous K<sub>ATP</sub> Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families
DateJanuary 1st, 2020
Issue nameHormone Research in Paediatrics
Issue numberv93.1 p58-65
DOI10.1159/000506476
AuthorsAmaratunga S, Hussein Tayeb T, Rozenkova K, Kucerova P, Pruhova S & Lebl J
MTGsMTG3
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