Melek Yildiz1, Teoman Akcay2, Banu Aydin2, Abdurrahman Akgun2, Beyza Belde Dogan2, Elisa De Franco3, Sian Ellard3, Hasan Onal2. 1. Istanbul Saglık Bilimleri Universitesi Kanuni Sultan Suleyman Egitim ve Arastırma Hastanesi, Cocuk Endokrinoloji Bolumu, 34303, Küçükçekmece, Istanbul, Turkey. 2. Department of Pediatric Endocrinology and Metabolism, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey. 3. Molecular Genetics University of Exeter Medical School, Exeter, Devon, UK.
Abstract
BACKGROUND: As KATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonylureas, empiric therapy is a common practice for NDM patients. CASE PRESENTATION: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo- and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a KATP channel mutation. However, this empiric sulfonylurea trial did not improve the patient's glycemic control and resulted in resistance to exogenous insulin. Genetic testing identified a previously reported homozygous INS promoter mutation (c.-331C>G), which was not responsive to sulfonylurea therapy. CONCLUSIONS: In light of our results, we recommend to confirm the genetic diagnosis as soon as possible and decide on sulfonylurea treatment after a genetic diagnosis is confirmed.
BACKGROUND: As KATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonylureas, empiric therapy is a common practice for NDM patients. CASE PRESENTATION: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo- and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a KATP channel mutation. However, this empiric sulfonylurea trial did not improve the patient's glycemic control and resulted in resistance to exogenous insulin. Genetic testing identified a previously reported homozygous INS promoter mutation (c.-331C>G), which was not responsive to sulfonylurea therapy. CONCLUSIONS: In light of our results, we recommend to confirm the genetic diagnosis as soon as possible and decide on sulfonylurea treatment after a genetic diagnosis is confirmed.
Authors: Sarah E Laurenzano; Cory McFall; Linda Nguyen; Dipal Savla; Nicole G Coufal; Meredith S Wright; Mari Tokita; David Dimmock; Stephen F Kingsmore; Ron S Newfield Journal: Cold Spring Harb Mol Case Stud Date: 2019-08-01