hrp0095p1-287 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2022

Hyperinsulinism secondary to PMM2 gene variants: a case series from a quaternary centre reporting associated inflammatory bowel disease and aortopathy.

Shaunak Meera , Bockenhauer Detlef , Flanagan Sarah , Kiparissi Fevronia , Jones Kelsey , Gilbert Clare , Morgan Kate , Dastamani Antonia

Introduction: A promoter mutation (c.167G>T) in the phosphomannomutase 2 (PMM2) gene, either homozygous or occurring in trans with a PMM2 coding mutation, causes hyperinsulinism (HI) and polycystic kidney disease (PKD) – HIPKD. Organ-specific deficiency of PMM2 leads to the restricted phenotype of HIPKD, without typical clinical features of the Congenital Disorder of Glycosylation Type 1a (CDG1a), which is caused by recessive coding ...

hrp0095p1-315 | Growth and Syndromes | ESPE2022

A Novel PADI6 Variant as a Cause of Recurrent Miscarriage and Multi Locus Imprinting Disturbance within the same family

Stern Eve , Goldman Shira , De Franco Elisa , E Flanagan Sarah , Pinhas-Hamiel Orit , Regev Miriam

Background: Genomic imprinting is the process by which preferential methylation of one parental allele results in parent of origin specific expression of particular genes. Methylation is established during gametogenesis and is maintained throughout development. Alterations in any of the processes in the establishment and maintenance of methylation can lead to aberrant imprinting, which can result in either reactivation of the original silent allele or the sile...

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...

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...

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...

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...

hrp0084p3-1080 | Hypo | ESPE2015

Severe Congenital Hyperinsulinism in a Neonate Homozygous for Two Novel Missense Mutations in the KCNJ11 Gene

Ozon Alev , Alikasifoglu Ayfer , Ellard Sian , Flanagan Sarah , Gonc Nazli , Orhan Diclehan , Ekinci Saniye , Kandemir Nurgun

Background: Congenital hyperinsulinism (CHI) is a heterogenous disorder characterized by hyperinsulinaemic hypoglycaemia, and may present in the neonatal period in severe forms of the disease. Molecular defects involving eight genes has been described so far. Herein we report a case of severe, diazoxide unresponsive CHI caused by two homozygous novel missense mutations in the KCNJ11 gene.Case report: An 8-day old girl was referred for hyperinsul...