hrp0084fc14.1 | Puberty | ESPE2015

KLB, Encoding the Co-receptor for FGF21, is Mutated in Congenital Hypogonadotropic Hypogonadism

Xu Cheng , Miraoui Hichem , Somm Emmanuel , Kinnunen Tarja , Dwyer Andrew , Preitner Nadia , Sykiotis Gerasimos , Santini Sara , Quinton Richard , Plummer Lacey , Crowley William , Hauschild Michael , Phan-Hug Franziska , Sidis Yisrael , Mohammadi Moosa , Messina Andrea , Pitteloud Nelly

Background: The hepatokine FGF21 signals through a dual receptor complex consisting of FGFR1c and the obligatory co-receptor β-Klotho to regulate glucose and lipid metabolism. Interestingly, female mice with Fgf21 transgenic overexpression are not only resistant to high-fat diet induced obesity but also present with hypogonadotropic hypogonadism (HH) and infertility. Loss-of-function (LOF) mutations in FGFR1 are a frequent cause of congenital HH (CHH). W...

hrp0084p2-530 | Puberty | ESPE2015

Nephrogenic Diabetes Insipidus with Partial Response to Ddavp Caused by a Novel AVPR2 Splice Site Mutation

Schernthaner-Reiter Marie Helene , Adams David , Nilsson Ola , Trivellin Giampaolo , Ramnitz Mary Scott , Raygada Margarita , Golas Gretchen , Faucz Fabio R. , Dileepan Kavitha , Lodish Maya B. , Lee Paul R. , Markello Thomas C. , Tifft Cynthia J. , Gahl William A. , Stratakis Constantine A.

Background: Congenital diabetes insipidus (DI) can be due to mutations in the arginine vasopressin (AVP) gene (familial neurohypophyseal DI), the AVP receptor type 2 (AVPR2) or aquaporin 2 (AQP2) genes (congenital nephrogenic DI, NDI). The clinical manifestation of congenital NDI, especially the response to AVP, can vary greatly depending on the functional effect of the AVPR2 mutation. Here we present two male siblings with NDI and partial response to ddAVP.<p class="abste...

hrp0092fc15.1 | Late Breaking Abstracts | ESPE2019

DLG2 Mutations in Patients with Delayed or Absent Puberty

Jee Youn Hee , Won Sehoon , Lui Julian C. , Jennings Melissa , Whalen Philip , Yue Shanna , Cheetham Tim , Boden Matthew G. , Radovick Sally , Quinton Richard , Leschek Ellen W. , Aguilera Greti , Yanovski Jack A. , Seminara Stephanie B. , Roche Katherine W. , Crowley William F. , Delaney Angela , Baron Jeffrey

NMDA (N-Methyl-D-aspartic acid) receptors have been shown to control the timing of sexual maturation in laboratory animals. Therefore, variants in genes impacting NMDA receptor signaling might be predicted to affect human puberty. We studied an extended family with extremely delayed puberty (menarche at 16.5 - 18 years for female family members and pubertal onset at 16 years for male family members). Exome sequencing revealed a rare missense variant (F900V) in DLG2, w...

hrp0089rfc9.5 | Pituitary, Neuroendocrinology and Puberty 1 | ESPE2018

Non-Isolated Central Precocious Puberty: Prevalence of Brain Lesions and Other Associated Disorders

Wannes Selmen , El Maleh Monique , De Roux Nicolas , Zenaty Delphine , Simon Dominique , Martinerie Laetitia , Storey Caroline , Gelwane Georges , Paulsen Anne , Ecosse Emmanuel , Jean-claude Carel , Juliane Leger

Background: Non-idiopathic central precocious puberty (CPP) is caused by acquired or congenital hypothalamic lesions visible on magnetic resonance imaging (MRI), or associated with various complex genetic and/or syndromic disorders without visible lesions on MRI. We investigated the different types and prevalences of non-isolated CPP phenotypes in a large group of consecutive patients with CPP.Methods: This observational cohort study included all patient...

hrp0086wg4.2 | ESPE Bone and Growth Plate Working Group (BGP) | ESPE2016

Hypercalcaemic Disorders in Children

Thakker Rajesh V.

Hypercalcaemic disorders in children may present with poor feeding, hypotonia, lethargy, dehydration, vomiting, polyuria, failure to thrive, seizures and hypertension. The causes of hypercalcaemia in children, which can be classified as parathyroid hormone (PTH)-dependent or PTH-independent, are similar to those occurring in adults except that primary hyperparathyroidism and malignancy which the most common causes in adults, and account for >90% of adult patients with hype...

hrp0089p3-p203 | GH &amp; IGFs P3 | ESPE2018

Results of Mecasermin Treatment in Pediatric Patients Evaluated for Severe and Partial Primary Deficiency of IGF-1

Stozek Karolina , Bossowski Artur

Background: Severe primary deficiency of insulin-like growth factor-1 (IGFD) being characterized by growth failure and short stature in children, constitutes an indication to recombinant human IGF-1 (mecasermin) treatment. It is defined by serum insulin-like-growth factor-1 (IGF-1) levels less than or equal to 2.5 th percentile, height less than or equal to −3 S.D.S., normal growth hormone (GH) secretion and exlusion of secondary causes of IGFD.<p clas...

hrp0095fc2.3 | Bone, Growth Plate and Mineral Metabolism | ESPE2022

First interim analysis of the International X-Linked Hypophosphataemia (XLH) Registry: Baseline characteristics of children treated with conventional therapy and burosumab

Boot Annemieke , Liu Jonathan , Williams Angela , Wood Sue

Objectives: X-linked hypophosphataemia (XLH) is a rare, hereditary phosphate-wasting disorder characterised by excessive activity of fibroblast growth factor 23. The International XLH Registry (NCT03193476) (initiated in August 2017, target 1,200 children and adults with XLH, running for 10 years) will provide information on the natural history of XLH and impact of treatment on patient outcomes. This report summarises baseline data from the first interim analy...

hrp0095p1-44 | Diabetes and Insulin | ESPE2022

Characterisation of Type 2 Diabetes mellitus in children and young people across 2 large tertiary Paediatric Diabetes centres

Chatterjee Sumana , Baioumi Alaa , Pryce Rebekah , Williams Georgina , Giri Dinesh

Introduction: The prevalence of paediatric Type 2 diabetes (T2DM) is increasing, contributed by rising incidence of obesity worldwide. Paediatric T2DM is a progressive disease with increased risk of complications and morbidities. Despite recent research, many aspects such as its pathophysiology and optimal management remain unknown.Aim: To characterise the cohort of T2DM patients across 2 large tertiary paediatric diabet...

hrp0092fc1.5 | Diabetes and Insulin Session 1 | ESPE2019

FADES: A Birth Cohort to Understand the Mechanisms Underlying Accelerated Onset of Autoimmunity in Children with Down's Syndrome

Williams Georgina , Mortimer Georgina L. , Leary Sam D. , Williams Alistair J.K. , Gillespie Kathleen M. , Hamilton - Shield Julian P.

Background and Aims: Children with Down's syndrome (DS) are at increased risk of autoimmune conditions including type 1 diabetes (T1D), coeliac and thyroid disease. We previously examined the clinical and immunogenetic characteristics of these conditions in children with DS. An earlier age-of-onset of diabetes was observed compared with children with T1D from the general population despite having decreased frequencies of the established genetic susceptibil...

hrp0084fc11.6 | Neuroendocrinology | ESPE2015

Long-term Outcome of Patients Treated for Paediatric Cushing’s Disease

Yordanova Galina , Lee Martin , Afshar Farhad , Sabin Ian , Alusi Ghasan , Plowman Nicholas , Evanson Jane , Matson Mattew , Grossman Ashley , Akker Scott , Monson John , Drake Wiliam , Savage Martin , Storr Helen

Background: Due to the rarity of Paediatric Cushing’s disease (CD) there is limited data on the long-term consequences of treatment.Objective and hypotheses: We assessed recurrence, anterior pituitary function and psychiatric disorders in a group of paediatric CD patients treated in a single centre.Method: Retrospective review of 20 patients with CD, mean age 11.75 years (5.74–17.8), managed in our centre between 1986 and...