ESPE Abstracts

Monogenic autoimmune diabetes results from a single highly penetrant mutation that causes autoimmunity leading to destruction of the beta-cells. Identifying monogenic autoimmune diabetes can be a challenge; early-onset type 1 diabetes (T1D) can cluster with additional autoimmune diseases due to shared polygenic risk, particularly from the HLA DR3 and DR4 alleles, and islet and other organ specific autoantibodies are present in patients with both monogenic and polygenic aetiolo...

Introduction: De novo and inherited cases of 16p11.2 microdeletion and duplication syndromes have a spectrum of clinical manifestations, with incomplete penetrance and variable expressivity.16p11.2 copy number variants have shared phenotypic features (autism, developmental delay). Mirror phenotypes have also been described: deletions – obesity, hyperphagia, macrocephaly; duplications – underweight, feeding/eating disor...

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 a rare heterogeneous disease. Genetic testing is crucial as identifying the underlying aetiology can guide clinical management.Objective and hypotheses: We investigated the clinical characteristics and genetics of 20 Ukrainian patients with CHI.Methods: Routine clinical and laboratory investigations were performed on 20 patients with hypoglycemia and unsuppressed C-peptide and p-insul...

Background: Wolcott–Rallison syndrome (WRS) which is characterized with permanent neonatal diabetes mellitus (PNDM), epiphyseal dysplasia, recurrent hepatitis and is caused by EIF2AK3 mutations.Objective and hypotheses: There is a possibility of a variant form of WRS, not caused by EIF2AK3 mutation.Method: Case 1: She was born at term from consanguineous parents. Family history was unremarkable. She had been ...

Background: Congenital hyperinsulinism (CHI) has not been studied in the Ukraine.Objective and hypotheses: We investigated the genetic aetiology and treatment of patients with CHI.Method: Routine clinical and laboratory investigations were performed in children with hypoglycaemia. Genetic testing was undertaken for seven patients with CHI from 9 families. KCNJ11, ABCC8, HNF4A genes were sequenced in all patients. For those...

Background: Hyperinsulinaemic Hypoglycaemia (HH) is a rare genetic disease and the treatment of HH in cases with unresponsiveness to medical therapy is subtotal pancreatectomy. In a recent study, the authors showed that sirolimus could be an alternative treatment in these patients. We aimed to evaluate the effectiveness of sirolimus in a newborn with HH.Case: A 10 day-old neonate presented with hyperinsulinaemic hypoglycaemia (glucose: 26 mg/dl, insulin:...

Introduction: Congenital hyperinsulinism (CHI) is a disorder of pancreatic beta-cells characterized by inappropriate secretion of insulin leading to hyperinsulinemic hypoglycemia. Insulin secretion is a complex, genetically regulated process. Mutations in several genes known to regulate insulin secretion result in CHI. Recently, non-coding mutations in HK1, which cause the aberrant expression of hexokinase 1 (HK1) in beta cells, have been reported as a novel c...

Introduction: Mutations in Insulin Receptor (INSR) is usually associated with insulin resistance and hyperglycemia. Homozygous or compound heterozygous mutations in INSR are usually linked with Rabson-Mendenhall or Donohue syndromes whilst heterozygous INSR mutations are associated with type A insulin resistance. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycemia (HH) have been de...

Background: Hyperinsulinaemic hypoglycaemia (HH) is a clinically and genetically heterogeneous group of disorders characterized by persistent hypoglycaemia due to inappropriate insulin secretion from the pancreatic β-cell.Aim: The objective was to analyze the demographic, clinical and genetic characteristics of patients with HH, diagnosed and/or treated at a tertiary endocrine center, part of the European referen...