hrp0082s3.2 | Novel Insights into Monogenic Diabetes | ESPE2014

Neonatal Diabetes: New Genes, New Mechanisim, New Phenotypes

Ellard S

Recent years have seen significant progress towards defining the genetic aetiology of neonatal diabetes with >20 subtypes identified. It is likely that all cases of neonatal diabetes result from a single gene disorder since markers of autoimmunity associated with type 1 diabetes are rare in patients diagnosed before 6 months.Heterozygous activating mutations in the KCNJ11 and ABCC8 genes encoding the Kir6.2 and SUR1 subunits of the ...

hrp0082p3-d1-875 | Perinatal and Neonatal Endocrinology | ESPE2014

Clinical Remission in a Patient with Congenital Hyperinsulinism due to Paternally Inherited Two Novel Mutations in KCJN11 Gene

Cebeci Ayse Nurcan , Houghton Jayne , Ellard Sian

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). ...

hrp0084p3-1066 | Hypo | ESPE2015

Congenital Hyperinsulinism in a Newborn with a Novel Paternally Inherited Heterozygous Mutation (p.E1517G) in the ABCC8 Gene

Elbarbary Nancy , Ellard Sian , Hussain Khalid

Background: Congenital hyperinsulinism (CHI), a clinically and genetically heterogeneous disease, is the most common cause of persistent hypoglycaemia in infancy.Case presentation: Here we describe an Egyptian male neonate first order of birth born to non-consanguineous healthy parents. At day 1 of age he presented with severe hypoglycemia and generalised seizures. At the time of hypoglycaemia (16 mg/dl) insulin and C-peptide levels were increased (insul...

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 ...

hrp0084p2-487 | 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...

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...

hrp0086p1-p553 | Perinatal Endocrinology P1 | ESPE2016

Neonatal Diabetes in Ukraine

Globa Eugenia , Zelinska Nataliya , Temple Karen , Mackay Deborah , Hattersley Andrew , Flanagan Sarah , Ellard Sian

Background: We established a neonatal section of the Ukrainian Pediatric Diabetes Registry (UPDR) to identify cases of neonatal diabetes (ND).Objective and hypotheses: We investigated the genetic etiology and treatment of patients with ND.Method: According to the UPDR the number of children (0–17 y.o) with DM1 in 2015 was 8388 (a prevalence of one in 907), with DM2 – 36 (one in 211519) and with ND – 52 (one in 146436...