ESPE Abstracts

Short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterized by diazoxide-responsive hyperinsulinemic hypoglycemia in the neonatal or infancy periods. These patients have severe protein (especially leucine) sensitivity. HADH mutations are recessively inherited with less than 50 patients reported so far. The mechanism behind unregulated insulin secretion in SCHAD deficiency is not understood but may involve changes in protein-protein interactions with glutamate deh...

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent and profound hypoglycemia in infants. There are two distinct histologic forms of CHI, diffuse and focal. The distinction between these forms is important in patients who fail medical therapy since surgical strategies may vary. Focal lesions occur due to paternally inherited recessive mutation in ABCC8 or KCJN11 genes with somatic loss of the maternal 11p15 region (paternal uniparental disomy). ...

Background: Congenital hyperinsulinism is a frequent cause of persistent hypoglycaemia in neonates. Mutations of the KATP channel subunit are the most common molecular defects. We report here a novel ABCC8 gene mutation causing a severe form of CHI in a newborn.Case report: A 10-day-old boy born to consanguineous parents was referred for persistent hypoglycaemia. He was born by normal vaginal delivery at 38 weeks gestation, birth weight was 4....

Background: Neonatal diabetes is a rare disease having usually a genetic origin. Defects in KCNJ11, ABCC8, INS, GCK, and PDX1 genes are more frequent and may lead non-transient, non-syndromic neonatal diabetes, whereas defects in PTF1A, FOXP3, EIF2AK3, GLIS3, RFX6, and NEUROD1 genes are very rare and may lead neonatal diabetes as a part of a syndrome.Objective and hypotheses: We present a patient with GLIS3 ge...

Background: In this study we investigated mortality in children with monogenic diabetes.Methods: Within the Ukrainian Pediatric Diabetes Register (UPDR) the number of children with type 1 diabetes mellitus (DM1) 0-17 y.o. in 2019 was 9860 (1 in 769), with DM2 - 36 (1 in 210,547) with neonatal DM (NDM) - 66 (1 in 115,000), with MODY - 40 cases (1 in 114,844). We used targeted next generation sequencing (tNGS) of all known...

Background: Hyperinsulinism is characterised by inappropriate insulin secretion during hypoglycaemia. Mutations in the KATP channel genes, ABCC8 and KCNJ11, are the most common cause of persistent congenital hyperinsulinism. The diagnosis of KATP hyperinsulinism is key for the clinical management of the condition.Aim: We aimed to determine the clinical features that help to identify KATP hyperinsulinism...

Background: Congenital hyperinsulinism (HI) is characterised by inappropriate insulin secretion despite low blood glucose which is commonly diagnosed in infancy (before the age of 12 months). Screening of the >20 known genes identifies a mutation in over 45% of cases. The likelihood of identifying a mutation in a known gene in individuals diagnosed after 12 months is not currently known.Aim: We aimed to identify the ...

Background and Aims: Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. The disease may occur in isolation or can present as part of a syndrome. Routine screening of the known etiological genes (n = >20) identifies a disease-causing mutation in 40-50% of all cases. An accurate and timely genetic diagnosis is clinically important for all individuals as understanding the unde...

The ATP-sensitive potassium (KATP) channel couples beta cell electrical activity to glucose-stimulated insulin secretion. Loss-of-function variants in either the regulatory (sulfonylurea receptor 1, encoded by ABCC8) or the pore-forming (inwardly rectifying potassium channel 6.2 [Kir6.2], encoded by KCNJ11) subunits result in congenital hyperinsulinism (CHI), whereas gain-of-function mutations cause neonatal diabetes. Patients with two recessive loss-of-funct...

Introduction and Aim: Congenital hyperinsulinism (CHI) is the most common cause of hypoglycaemia in early infancy and represents a heterogeneous disorder with respect to clinical presentation, histology and genetics. The aim of our study is to review correlation between genotype and phenotypic characteristics of children with CHI.Methods: Retrospective review of CHI patients with positive genetics during the last 8 years...