hrp0092p1-319 | Diabetes and Insulin (2) | ESPE2019

Gene Dosage Changes in the GCK Gene not Detected by Sanger DNA Sequencing in Two Patients with Phenotypic MODY 2

Birkebaek Niels H. , Brusgaard Klaus

Background: Maturity onset diabetes of the young 2 (MODY2) is phenotypically characterized by elevated fasting and post-prandial blood glucose (BG) levels and no diabetes auto-antibodies. Inheritance is autosomal dominant, and it is caused by variants in the glucokinase (GCK) gene with resetting of the pancreatic glucose sensor to a higher level. It is essential to detect MODY 2 patients as they do not require treatment.Objective...

hrp0086p1-p222 | Diabetes P1 | ESPE2016

Transient, Neonatal Hyperinsulinemic Hypoglycemia May be Monogenetic, Not Only Secondary to Fetal Life Events

Olesen Louise , Jacobsen Anne , Brusgaard Klaus , Christesen Henrik

Background: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with a transient, recurrent or persistent course. Transient CHI (tCHI) is considered to be caused by non-genetic risk factors e.g. birth asphyxia and intrauterine growth restriction (IUGR), while persistent hyperinsulinism is known to be caused by mutations in at least nine genes: ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A and UCP2.Objective and hy...

hrp0097rfc9.2 | Diabetes and insulin 2 | ESPE2023

Two new candidate genes, OGDH and FGFR1 discovered in an insulinoma from a fifteen-year-old male

Andersen Kirstine , Brusgaard Klaus , Detlefsen Sönke , Christesen Henrik

The present study aimed to determine the mutational and molecular landscape of a 17 mm insulinoma from a fifteen-year-old male. Using targeted exome sequencing and microarray, we investigated somatic candidates in the insulinoma. The microarray analysis was conducted using 12 other insulinomas as a control group and revealed a total of 1907 differentially expressed genes (P-value < 0.05, FDR P-value < 0.05). After thorough gene variant filtering, we ide...

hrp0089p2-p073 | Diabetes &amp; Insulin P2 | ESPE2018

A Novel Mutation in Phka2: Idiopathic Ketotic Hypoglycaemia May Represent Mild Gsdixa

Flejsborg Anne Benner , Brusgaard Klaus , Pedersen Carsten , Frederiksen Anja L , Christesen Henrik T

Background: Idiopathic ketotic hypoglycaemia (IKH) is an exclusion diagnosis and the most common cause of hypoglycaemia in childhood. Glycogen Storage disease (GSD) type IX comprises one quarter of all GSD’s. GSDIXa, encoded by PHKA2, is the most frequent subtype.Objective: To investigate whether IKH may be undiagnosed GSDIXa.Methods: Hospital file review and next generation sequence 29 gene GSD-panel.<p class="ab...

hrp0089p3-p172 | Fetal, Neonatal Endocrinology and Metabolism P3 | ESPE2018

Forty patients with persistent, non-focal congenital hyperinsulinism: Urgent need for new treatment modalities

Rasmussen Amalie Greve , Melikian Maria , Globa Evgenia , Detlefsen Sonke , Rasmussen Lars , Petersen Henrik , Brusgaard Klaus , Rasmussen Annett Helleskov , Christesen Henrik

Background: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with a focal, diffuse, or atypical histological form and a high risk of cerebral injury due to severe hypoglycemia.Methods: We retrospectively evaluated the treatment and outcome of a cohort of patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark from January 2000 to May 2017. Data were extracted from hospital files.<p class=...

hrp0086p1-p558 | Perinatal Endocrinology P1 | ESPE2016

Cerebral Outcome of Children with Congenital Hyperinsulism

Rasmussen Annett Helleskov , Melikian Maria , Portner Fani , Larsen Anna-marie , Scherderkina Inna , Globa E , Filipsen Karen , Brusgaard Klaus , Christesen Henrik

Background: Congenital hyperinsulinism (CHI) is a rare condition characterized by unregulated secretion of insulin from pancreatic islet β cells. The primary treatment goal is to obtain normoglycemia, since hypoglycemia in the neonatal period can have severe impact on cerebral development.Objective and hypotheses: To assess the cerebral function in children with CHI at follow up.Method: From an international cohort, 40 childre...

hrp0092p1-211 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) (1) | ESPE2019

Characteristics of Children with Kabuki Syndrome and Hyperinsulinemic Hypoglycemia

Hoermann Henrike , El-Rifai Omar , Schebek Martin , Brusgaard Klaus , Bachmann Nadine , Bergmann Carsten , Mayatepek Ertan , Christesen Henrik , Meissner Thomas , Kummer Sebastian

Background: Kabuki syndrome (KS) is a rare multiple congenital malformation and intellectual disability syndrome. KS is caused by pathogenic variants in the genes KMT2D or KDM6A. In 0.3-4% of patients, KS is reported to be associated with hyperinsulinemic hypoglycemia. The objective of this study was to characterize the clinical, biochemical and molecular data of children with KS and hyperinsulinemic hypoglycemia.<s...

hrp0084p3-1063 | Hypo | ESPE2015

Genotype–Phenotype Associations in 90 Children with Congenital Hyperinsulinism

Melikyan Maria , Christesen Henrik , Petryakina Elena , Tulpakov Anatoly , Tihonovich Julia , Stepanov Alexey , Kareva Maria , Flanagan Sarah , Ellard Sian , Brusgaard Klaus , Peterkova Valentina , Hussain Khalid

Background: Congenital hyperinsulinism (CHI) is a common cause of hypoglycaemia in neonates, infants and children. CHI is a heterogeneous disease in terms of clinical presentation, genetics and histology.Objective and hypotheses: The aim of this study was to describe the clinical characteristics, genotype–phenotype correlations and treatment outcome of Russian patients with CHI.Method: A total of 90 children with CHI were iden...

hrp0097rfc10.5 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) &amp; Multisystem endocrine disorders | ESPE2023

Insulinoma in childhood: A multicenter retrospective study of 28 patients

Melikyan Maria , Gubaeva Diliara , Shadrina Anna , Bolmasova Anna , Kareva Maria , Tiulpakov Anatoly , Gurevich Larisa , Efremenkov Artem , Averyanova Julia , Andersen Kirstine , Brusgaard Klaus , Detlefsen Sonke , Christesen Henrik

Background: Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).Methods: We conducted a multicentre retrospective review of patients diagnosed with insulinoma between 1995-2021. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.<p class="abste...

hrp0094fc4.6 | Diabetes | ESPE2021

Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort

McGlacken-Byrne Sinead M. , Mohammad Jasmina Kallefullah , Conlon Niamh , Gubaeva Diliara , Siersbaek Julie , Jorgen Schou Anders , Demibilek Huseyin , Dastamani Antonia , Houghton Jayne , Brusgaard Klaus , Melikyan Maria , Christesen Henrik , Flanagan Sarah E. , Murphy Nuala P. , Shah Pratik ,

Objective: The complex clinical phenotypes arising from HNF4A and HNF1A mutations are similar and include diazoxide-responsive CHI from infancy and maturity-onset diabetes of the young (MODY) from adolescence. We aimed to characterise the clinical and genetic aspects of a cohort of paediatric patients with HNF4A or HNF1A mutations.Methods: Patients from five international centres over ...