hrp0097fc2.4 | Bone, Growth Plate and Mineral Metabolism | ESPE2023

A real-world study in Germany and Switzerland regarding renal health in children with X-linked hypophosphatemia

Böckmann Ineke , Leifheit-Nestler Maren , John Ulrike , Metzing Oliver , Rehberg Mirko , Peter Schlingmann Karl , Kemper Markus , Patzer Ludwig , Weitz Marcus , Wühl Elke , Freiberg Clemens , Sparta Giuseppina , Hiort Olaf , Schnabel Dirk , Hoppe Bernd , Haffner Dieter

Purpose: X-linked hypophosphatemia (XLH) is the most common hereditary cause of hypophosphatemic rickets. Elevated circulating levels of fibroblast growth factor 23 (FGF23) caused by mutations in the PHEX gene lead to renal phosphate wasting and rickets. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis in XLH patients. Mice on a high phosphate diet develop proximal tubular injury. Detailed analysis on kidney ...

hrp0097fc7.2 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2023

Mapping the transcriptomic landscape of early human fetal ovary development through a clinically-focused lens

M McGlacken-Byrne Sinead , Del Torres Ignacio , P Suntharalingham Jenifer , Buonocore Federica , HDBR ICH , Crespo Berta , Moreno Nadjeda , C Simcock Ian , Arthurs Owen , Xenakis Theodoros , Niola Paola , Brooks Tony , T Dattani Mehul , C Achermann John

Introduction: Ovary development was once considered a largely passive process. RNA sequencing (RNAseq) approaches have allowed us to begin to characterise ovary development in previously unparalleled detail, revealing the process to be complex and, still, little understood. A challenge is synthesising and using these data to advance our understanding of clinical disease. Through a clinically-focused lens, we elucidate novel aspects of the transcriptional lands...

hrp0098fc5.3 | Growth and Syndromes | ESPE2024

Gene expression of monosomy × during human development reveals potential mechanisms in Turner syndrome

Suntharalingham Jenifer , Del Valle Ignacio , Buonocore Federica , McGlacken-Byrne Sinead , Brooks Tony , Ogunbiyi Olumide , Liptrot Danielle , Dunton Nathan , Madhan Gaganjit , Metcalfe Kate , Nel Lydia , Marshall Abigail , Ishida Miho , Sebire Neil , Moore Gudrun , Crespo Berta , Solanky Nita , Conway Gerard , Achermann John

Background: Monosomy × (45,X) is associated with Turner syndrome (TS) and pregnancy loss; however, the underlying mechanisms remain unclear. Girls and young women with TS/45,X can present with diverse clinical features and at different ages, including early postnatal life, suggesting that at least some mechanisms may be defined during early fetal development.Aims: To explore transcriptomic expression profiles in ke...

hrp0098fc15.2 | Late Breaking | ESPE2024

Amount and Pattern Of Pulsatile GH Secretion Induced By The Oral Growth Hormone Secretagogue LUM-201 Is Related To Growth And IGF-1 Responses In Moderate Pediatric Growth Hormone Deficiency (PGHD)

Roslan Amirul , Román Rossana , Avila Alejandra , Said Daniela , Baier Ingrid , L. Brincks Erik , Bruchey Aleksandra , C. McKew John , Duke Pitukcheewanont Pisit , L. Johnson Michael , Garner Terence , O. Thorner Michael , E. Clayton Peter , Stevens Adam , Cassorla Fernando

Background: Oral LUM-201 normalizes growth rates in moderate PGHD over 12 months (Phase 2 Trials: OraGrowtH210/OraGrowtH212) [FC-746 ESPE 2024]. In OraGrowtH212, GH profiles, based on 10-minute sampling over 12 hours (8am-8pm), showed significant increases in inter-pulse, pulsatile and total GH secretion in response to 1.6 and 3.2 mg/kg/day doses of LUM-201 over 6 months, with no difference between the doses [FC14.3, ESPE 2023].O...

hrp0098p1-185 | Pituitary, Neuroendocrinology and Puberty 3 | ESPE2024

Genetic analysis of a European cohort of ROHHAD patients

Buonocore Federica , Cerbone Manuela , Brooks Tony , Guftar Shaikh M , Heffernan Emmeline , Montero Raúl , Galcheva Sonya , Iotova Violeta , Mohamed Zainaba , Napoli Flavia , Anderson John , Maghnie Mohamad , T. Dattani Mehul

Introduction: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare life-limiting paediatric condition, with about 200 reported cases worldwide. The disease typically presents in early childhood (1.5-5y) with rapid-onset obesity. Other clinical symptoms may include central hypoventilation, hypothalamo-pituitary (H-P) dysfunction (hyperprolactinaemia, salt-water imbalances, anterior pituitary deficits...

hrp0098p2-338 | Late Breaking | ESPE2024

Reducing BMI below the obesity threshold in children aged 6 to <12 years treated with once-daily liraglutide 3.0 mg: A secondary analysis of the SCALE Kids study

K. Fox Claudia , Barrientos-Pérez Margarita , M. Bomberg Eric , Dcruz John , Gies Inge , Majlund Harder-Lauridsen Nina , Yazid Jalaludin Muhammad , Sahu Kushal , Weimers Petra , Zueger Thomas , Arslanian Silva

Childhood obesity is associated with present and future complications, including type 2 diabetes and cardiovascular disease. Although lifestyle interventions (i.e. dietary and physical activity counselling) are the cornerstone of therapy, their impact on body mass index (BMI) is limited. The phase 3a SCALE Kids study (NCT04775082) demonstrated superiority of liraglutide 3.0 mg versus placebo, plus lifestyle interventions, for BMI reduction in children with general (i.e. non-mo...

hrp0094p2-19 | Adrenals and HPA Axis | ESPE2021

Genetic analysis of paediatric primary adrenal insufficiency of unknown aetiology over 25 years

Buonocore Federica , Maharaj Avinaash , Qamar Younus , Koehler Katrin , Suntharalingham Jenifer P. , Chan Li F. , Ferraz-de-Souza Bruno , Hughes Claire R. , Lin Lin , Prasad Rathi , Allgrove Jeremy , Andrews Edward T. , Buchanan Charles R. , Cheetham Tim D. , Crowne Elizabeth C. , Davies Justin H. , Gregory John W. , Hindmarsh Peter C. , Hulse Tony , Krone Nils P. , Shah Pratik , Shaikh Mohamad G. , Roberts Catherine , Clayton Peter E. , Dattani Mehul T. , Thomas N. Simon , Huebner Angela , Clark Adrian J. , Metherell Louise A. , Achermann John C. ,

Introduction: Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires appropriate diagnosis and treatment. The most common cause of PAI is congenital adrenal hyperplasia (CAH), but other well-established aetiologies include metabolic and autoimmune disorders, and physical damage. Mutations in more than 30 genes have now been associated with PAI, with considerable biochemical and phenotypic overlap. It is therefore importan...

hrp0095p1-306 | Growth and Syndromes | ESPE2022

Bone age in children with achondroplasia.

Savarirayan Ravi , Maria De Bergua Josep , Arundel Paul , Pierre Salles Jean , Leiva-Gea Antonio , Irving Melita , Saraff Vrinda , McDevitt Helen , Nicolino Marc , Cormier-Daire Valerie , Kannu Peter , Skae Mars , B. Bober Michael , Phillips III John , Burren Christine , Harmatz Paul , Saal Howard , Hoover-Fong Julie , Muslimova Elena , Cho Terry , Weng Richard , Rogoff Daniela

Background: Bone age (BA) is commonly used in pediatrics to define skeletal maturity for medical and non-medical purposes. Normal range is represented by 2 standard deviations (SDs) above and below the mean. A BA greater than &pm;2 SDs from the chronological age (CA) is considered abnormal. BA in achondroplasia (ACH) has not been fully characterized; calculation is challenging given difficulties in comparing x-rays with standard radiographs if using the Greuli...

hrp0086fc11.1 | Thyroid | ESPE2016

Mutations in TBL1X as a Novel Cause of Familial Central Hypothyroidism

Heinen Charlotte , Losekoot Monique , Sun Yu , Watson Peter , Fairall Louise , Joustra Sjoerd , Zwaveling-Soonawala Nitash , Oostdijk Wilma , van den Akker Erica , Santen Gijs , van Rijn Rick , Dreschler Wouter , Surovtseva Olga , Biermasz Nienke , Hennekam Raoul , Wit Jan , Schwabe John , Boelen Anita , Fliers Eric , van Trotsenburg Paul

Background: Congenital central hypothyroidism (CeH) may occur isolated, or in combination with other pituitary hormone deficiencies. Although a third causative gene for CeH was recently reported (IGSF1), the aetiology of isolated CeH has remained unexplained in most cases.Objective and hypotheses: We hypothesized that in three relatives with unexplained isolated CeH a mutation in another gene might be responsible for the phenotype.<p class="...

hrp0084ha2 | A New Syndrome Associated with Mutations in the Gene for Pregnancy-Associated Plasma Protein A2 (PAPP-A2) | ESPE2015

A New Syndrome Associated with Mutations in the Gene for Pregnancy-Associated Plasma Protein A2 (PAPP-A2) Causing Proportionate Short Stature, High Circulating IGF-I, IGFBP-3, and ALS, Mild Microcephaly, thin Long Bones and Decreased Bone Mineral Density in two Unrelated Families

Dauber Andrew , Munoz-Calvo Maria T , Barrios Vicente , Desikan Vardhini , Pozo Jesus , Muzumdar Radhika , Martos-Moreno Gabriel A , Hawkins Federico , Domene Horacio , Jasper Hector G , Kloverpris Soren , Yakar Shoshana , Conover Cheryl A , Kopchick John J , Hwa Vivian , Chowen Julie A , Oxvig Claus , Rosenfeld Ron G , Perez-Jurado Luis A , Argente Jesus

Background: PAPP-A2 is a metalloproteinase that specifically cleaves IGFBPs 3 and 5. Papp-a2 knock-out (KO) mice show a reduction in body size and skeletal abnormalities.Objective and hypotheses: Our objective is to report two affected families from Spain and USA. The Spanish family presents a homozygous frameshift mutation in exon 3 of the PAPP-A2 gene (c.1927_ 1928insAT, p.D643fs25X) resulting in a premature stop codon, with 2 of 4 si...