hrp0092s8.2 | Autoimmunity: From Diagnosis to Treatment | ESPE2019

Monogenic Forms of Autoimmune Diabetes: Challenges and Opportunities

Flanagan Sarah

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...

hrp0092p1-64 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Hyperinsulinaemic Hypoglycaemia: A New Presentation of 16p11.2 Duplication Syndrome

Conwell Louise , Flanagan Sarah

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...

hrp0084p2-487 | Hypo | ESPE2015

Congenital Hyperinsulinism in Ukraine

Globa Eugenia , Zelinska Nataliya , Flanagan Sarah , Ellard Sian , Christesen Henrik

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...

hrp0089p2-p184 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

20 Cases of Congenital Hyperinsulinism in Ukraine

Globa Evgenia , Zelinska Nataliya , Ellard Sian , Flanagan Sarah , Christesen Henrik

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...

hrp0082p3-d3-730 | Diabetes (2) | ESPE2014

Wolcott–Rallison Syndrome in Two Siblings with no Implication of EIF2AK3 Mutation

Altincik Ayca , Ozhan Bayram , Flanagan Sarah , Ellard Sian

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 ...

hrp0084p2-489 | Hypo | ESPE2015

The Effectiveness of Sirolimus in a Newborn with Hyperinsulinaemic Hypoglycaemia

Haliloglu Belma , Tuzun Heybet , Flanagan Sarah , Kaya Avni , Celik Muhittin

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:...

hrp0092fc9.2 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Heterozygous Insulin Receptor (INSR) Mutation associated with Neonatal Hyperinsulinaemic Hypoglycaemia and Familial Diabetes Mellitus

Sethi Aashish , Ahmed Syed Haris , Colclough Kevin , Didi Mohammed , Flanagan Sarah , Senniappan Senthil

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...

hrp0092p2-149 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Clinical and Genetic Characteristics of Patients with Hyperinsulinaemic Hypoglycaemia Diagnosed and Treated at a Tertiary Endocrine Center, a part of the ENDO-ERN

Galcheva Sonya , Iotova Violeta , Ellard Sian , Chuperkova Jivka , Bazdarska Yuliya , Bocheva Yana , Flanagan Sarah E.

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...

hrp0089fc10.5 | Late Breaking | ESPE2018

A 5-Year Single-Centre Experience on the Safety and Efficacy of Sirolimus Therapy used for the Treatment of Congenital Hyperinsulinaemic Hypoglycaemia

Guemes Maria , Dastamani Antonia , Ashworth Michael , Morgan Kate , Ellard Sian , Flanagan Sarah , Dattani Mehul , Shah Pratik

Background: Case reports have documented variable glycaemic response to the mTOR inhibitor Sirolimus in severe diazoxide+/−octreotide unresponsive forms of congenital hyperinsulinaemic hypoglycaemia (CHI). A high incidence of adverse effects has been reported in patients receiving this medication.Objective(s): To describe the efficacy and safety of Sirolimus use over a 5-year period in the largest cohort of CHI patients treated to date.<p class...

hrp0089p2-p187 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

A Boy with Diazoxide Unresponsive Congenital Hyperinsulinism due to a Homozygous ABCC8 Missense Mutation Previously Reported to be Dominant

Galcheva Sonya , Iotova Violeta , Flanagan Sarah E , Ellard Sian , Hattersley Andrew

Background: Congenital hyperinsulinism possesses considerable clinical heterogeneity attributed partly to its diverse genetic causes.Objective: To present a boy with diazoxide unresponsive hyperinsulinaemic hypoglycaemia due to a homozygous recessive ABCC8 missense mutation, previously reported to be dominant acting and being inherited by his unaffected heterozygous parents.Material and results: The boy was a third preterm child of...