hrp0089p2-p183 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

Congenital Hyperinsulinism: Management and Outcome in West of Scotland

Eltonbary Khadiga , Robinson Peter , Banerjee Indi , Shaikh Mohammed Guftar

Introduction: Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as Congenital Hyperinsulinism (CHI). Hypoglycaemia is the main feature of CHI, and early diagnosis and immediate management are essential to reduce the high risk of neurological damage. Diazoxide is the mainstay of medical treatment, with surgery being an option in appropriate cases.<p cl...

hrp0089p1-p191 | Multisystem Endocrine Disorders P1 | ESPE2018

SGPL1 Missense Mutation in an Infant with Primary Adrenal Insufficiency (PAI), Congenital Nephrotic Syndrome, Primary Hypothyroidism and Gonadal Failure

Maharaj Avinaash , Wallace Dean , Banerjee Indi , Prasad Rathi , Metherell Lou

Background: Loss of function mutations in SGPL1 have previously been described by our group in association with a multisystemic disorder encompassing PAI and nephrotic syndrome. SGPL1 encodes, sphingosine 1-phosphate lyase (SGPL1), which irreversibly binds sphingosine 1-phosphate (S1P) and commits it to the final degradative step in sphingolipid metabolism. SGPL1 is therefore a major modulator of S1P signalling. Several sphingolipid intermediates such as cera...

hrp0089p1-p250 | Thyroid P1 | ESPE2018

Thyroid Scintigraphy in the Diagnosis of Congenital Hypothyroidism

Woth Chris , Banerjee Indi , Hird Beverley , Patel Leena , Tetlow Lesley

Background: Identification of Congenital Hypothyroidism (CH) is an essential part of Newborn Bloodspot Screening (NBS) in the UK. NBS for CH relies on Blood Spot (BS) Thyroid Stimulating Hormone (TSH) measurement in newborns on day 5 of life. Diagnostic confirmation of a screen positive result requires measurement of plasma/serum free thyroxine (fT4) and TSH but technetium thyroid scanning is not mandatory. Technetium-99m scintigraphy can be used to define siz...

hrp0089rfc7.3 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2018

Central Venous Cathether-Associated Thrombosis in Children with Congenital Hyperinsulinism

Yau Daphne , Salomon-Estebanez Maria , Chinoy Amish , Murray Philip G , Banerjee Indi

Introduction: Congenital hyperinsulinism (CHI) is the most common cause of hypoglycaemia in infancy caused by dysregulated insulin secretion. The management of severe hypoglycaemia often requires the administration of high dextrose-containing fluids through a central venous catheter (CVC). However, CVCs carry the risk of complications including thrombosis. We sought to determine the incidence of CVC-associated thrombosis in patients with CHI and examine associated risk factors...

hrp0086rfc10.6 | Perinatal Endocrinology | ESPE2016

Increased Islet Cell Neogenesis and Endocrine Cell Differentiation in Congenital Hyperinsulinism in Infancy

Hardwick Elise , Han Bing , Salomon-Estebanez Maria , Padidela Raja , Skae Mars , Craigie Ross , Cosgrove Karen , Banerjee Indi , Dunne Mark

Background: Congenital Hyperinsulinism in Infancy (CHI) is characterised by inappropriate insulin release. We currently attribute hypoglycaemia to β-cell dysfunction because of defects in the ion channel genes ABCC8 or KCNJ11. However, the CHI pancreas is also associated with inappropriate expression of foetal-like transcription factors and enhanced cell proliferation.Hypothesis: As the CHI pancreas bears similarities to the foetal pancreas, we hypo...

hrp0086p1-p551 | Perinatal Endocrinology P1 | ESPE2016

Enhanced Mitochondrial Densities Associate with the Pathobiology of β-Cells in Congenital Hyperinsulinism in Infancy

Han Bing , Salomon-Estebanez Maria , Padidela Raja , Skae Mars , Kadler Karl , Cosgrove Karen , Banerjee Indi , Dunne Mark

Background: Congenital hyperinsulinism in infancy (CHI) is associated with inappropriate insulin release from β-cells. This is causally linked to defects in the ion channel genes ABCC8 and KCNJ11 regulating insulin, but little is known about the metabolic support for sustained insulin exocytosis.Objective and hypotheses: We hypothesised that inappropriate insulin release in CHI would require sustained ATP generation by enhanced mit...

hrp0086p1-p555 | Perinatal Endocrinology P1 | ESPE2016

Islet of Langerhans in Congenital Hyperinsulinism in Infancy are Disrupted and with Decreased Expression of Collagen (IV) α1 Chain in Basement Membranes

Mal Walaa , Salomon-Estebanez Maria , Padidela Raja , Skae Mars , Craigie Ross , Rigby Lindsey , Cosgrove Karen , Banerjee Indi , Dunne Mark

Background: Congenital hyperinsulinism of infancy (CHI) is the most common cause of severe hypoglycaemia in children. Although CHI arises from mutations in KATP channels which lead to inappropriate insulin secretion, CHI it also is associated with marked changes in islet organization.Aims and objectives: Our aim was to investigate the structure and composition of the islet capsule in CHI and age-matched control tissue.Me...

hrp0086p1-p549 | Perinatal Endocrinology P1 | ESPE2016

Congenital Hyperinsulinism in Infancy: The Profiles of Insulin Secretory Granules are Markedly Different in Focal- and Diffuse β-Cells

Han Bing , Mohamed Zainab , Salomon-Estebanez Maria , Padidela Raja , Skae Mars , Craigie Ross , Rigby Lindsey , Cosgrove Karen , Banerjee Indi , Dunne Mark

Background: The mechanisms responsible for inappropriate insulin release from β-cells in congenital hyperinsulinism in infancy (CHI) have largely focused upon defects in KATP channels. Little is known about insulin biogenesis, the profiles of insulin in insulin-containing secretory granules or whether the impact of KATP channel defects is the same in diffuse- and focal disease.Objective and hypotheses: To define the ultrastruct...

hrp0095p1-88 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2022

An Ongoing Phase 2 Study of HM15136, a Novel Long-acting Glucagon Analogue, in Subjects with Congenital Hyperinsulinism (ACHIEVE, Outline Protocol)

Shin Wonjung , Kang Jiyeon , Lee Grace , Maria Arbelaez Ana , Banerjee Indi , Dastamani Antonia , Mohnike Klaus , Okawa Erin , Cho Hyungjin , D De León Diva

Congenital hyperinsulinism (CHI) is an ultra-rare disease characterized by excessive insulin secretion that results in persistent hypoglycemia. If left untreated, CHI-induced severe prolonged hypoglycemia may lead to permanent neurologic damage. Currently used pharmacologic agents fail to prevent hypoglycemia in a subset of patients with CHI. HM15136 is a novel long-acting glucagon analogue that have demonstrated good stability and extended half-life ranging from 77 to 167 hou...