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...

hrp0084p1-103 | Perinatal | ESPE2015

Molecular Characterization of a Novel Non-stop KCNJ11 Mutation Associated with a Dual Focal and Diffuse Hyperinsulinaemic Hypoglycaemia Phenotype

Arya Ved Bhushan , Aziz Qadeer , Flanagan Sarah E , Ellard Sian , Tinker Andrew , Hussain Khalid

Background: Hyperinsulinaemic hypoglycaemia (HH) has two main histological subtypes: diffuse and focal. Diffuse HH are most commonly due to recessive or dominant ABCC8/KCNJ11 mutations. Focal HH results due to somatic loss of the maternal 11p allele involving the ABCC8 and KCNJ11 region in patients with paternally inherited ABCC8 or KCNJ11 mutation.Aim: To molecular characterise a novel non-stop KCNJ11</em...

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...

hrp0084p1-104 | Perinatal | ESPE2015

Diazoxide Responsive Congenital Hyperinsulinism in a Patient with Dual Genetic Aetiology (HNF4A and ABCC8 Mutation)

Giri Dinesh , Flanagan Sarah E , Park Julie , Ellard Sian , Didi Mo , Sennaippan Senthil

Background: Congenital hyperinsulinism (CHI) results from unregulated insulin secretion from pancreatic β-cells, which leads to persistent hypoglycaemia. Mutations in nine different genes are reported and phenotypic variability exists both within and between the genetic subgroups. Variable penetrance has been described in some families with the same mutation; for example HNF4A mutations cause neonatal hypoglycaemia and/or maturity onset diabetes of the young (MODY).<p...

hrp0094p2-244 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) | ESPE2021

Genetic Testing Access and Results for Patients with Congenital Hyperinsulinism as Conducted through the CHI and University of Exeter Partnership

Pasquini Tai L.S. , Houghton Jayne A.L. , Mesfin Mahlet , Flanagan Sarah E. , Raskin Julie ,

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...

hrp0084p2-486 | Hypo | ESPE2015

Transient Hyperinsulinaemic Hypoglycaemia in Association with a Novel ABCC8 Mutation: Expanding the Clinical Phenotypes

Arya Ved Bhushan , Aziz Qadeer , Mohamed Zainaba , Flanagan Sarah E. , Ellard Sian , Ehtisham Sarah , Tinker Andrew , Hussain Khalid

Background: Hyperinsulinaemic hypoglycaemia (HH) can be transient or permanent. Transient HH (spontaneous resolution of HH within few weeks) is associated with intrauterine growth restriction, maternal diabetes, erythroblastosis fetalis etc. Transient HH has not been reported with ABCC8/KCNJ11 mutations, which are the commonest cause of HH.Aim: Molecular characterisation of a novel ABCC8 mutation associated with a transient HH phenotype seen in a family ...

hrp0092rfc9.5 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Spectrum of Neuro-Developmental Disorders in Children with Congenital Hyperinsulinism Due to Activating Mutations in GLUD1

Aftab Sommayya , Gubaeva Diliara , Dastamani Antonia , Sotiridou Ellada , Gilbert Clare , Houghton Jayne , Flanagan Sarah E. , Melikyan Maria , Shah Pratik

Background & Objective: Hyperinsulinism-Hyperammonaemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism (CHI) in outbred populations. HI/HA is caused by an activating mutation in the GLUD1 gene which encodes the intra-mitochondrial enzyme glutamate dehydrogenase (GDH).The aim of this study was to determine the clinical presentation, treatment and risk factors of neuro-developmental disorders in ...

hrp0086p1-p554 | Perinatal Endocrinology P1 | ESPE2016

Clinical and Molecular Characteristics of Turkish Patients with Congenital Hyperinsulinism: A Single-Center Experience

Yildiz Melek , Akcay Teoman , Mutlu Neval , Akgun Abdurrahman , Onal Hasan , Ulucan Korkut , Ellard Sian , Flanagan Sarah E.

Background: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia which needs a prompt diagnosis and relevant treatment to avoid brain damage. So far, mutations in 11 key genes are known to cause monogenic forms of HI.Objective and hypotheses: The aim of this study was to characterize the clinical and molecular features of Turkish congenital HI patients and analyze the genotype/phenotype correlations.M...

hrp0084p1-30 | Diabetes | ESPE2015

A Novel Mutation in the abcc8 Gene Causing a Variable Phenotype of Impaired Glucose Metabolism in the Same Family

Maines Evelina , Hussain Khalid , Flanagan Sarah E , Ellard Sian , Piona Claudia , Morandi Grazia Grazia , Ben Sarah Dal , Cavarzere Paolo , Antoniazzi Franco Franco , Gaudino Rossella

Background: Dominantly acting loss-of-function mutations in the ABCC8 gene, encoding the sulfonylurea receptor 1 (SUR1) subunit of the β-cell potassium channel (KATP), are usually responsible for mild diazoxide-responsive congenital hyperinsulinism (CHI). In rare cases dominant ABCC8 mutations can cause diffuse diazoxide-unresponsive CHI. Recent reports suggest that medically responsive CHI due to a dominant ABCC8 mutation may confer an increase...

hrp0089p2-p182 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

Clinical Characterstics, Genotype-Phenotype Correlations and Follow Up of Patients with Congenital Hyperinsulinaemic Hypoglycaemia; Single Center Experience from a Southeastern City of Turkey

Ozbek Mehmet Nuri , Demirbilek Huseyin , Haliloglu Belma , Demiral Meliha , Baran Riza Taner , Ellard Sian , Houghton Jayne , Flanagan Sarah E , Hussain Khalid

Objective: Congenital Hyperinsulinism (CHI) is a clinically, genetically and histologically heterogenous diesease. In recent years substantial developements have been observed in the genetics, imaging techniques and treatment options. We herein present the clinical characteristics, genetics and follow-up of 31 CHI patients from a single paediatric endocrine center with a particular emphasis on the new treatment options.Patients and method: Clinical chara...