hrp0097p1-366 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2023

Trends in diagnosis and management of children with Differences in Sex Development over three decades– clinical experience of a tertiary care center

Eben Chaime Amit , Phillip Moshe , Ben-Meir David , de Vries Liat

Introduction: Differences in sex development (DSD) comprise a heterogeneous group of congenital conditions that affect human sex determination and differentiation. We aimed to describe the clinical diagnoses of children with DSD who were referred to a pediatric tertiary center, and to examine trends in clinical features and management over three decades.Methods: This is a retrospective, cross-sectional study of children ...

hrp0098p1-291 | Thyroid 3 | ESPE2024

Response to TRIAC therapy in a child with Resistance to Thyroid Hormone beta and behavioural abnormalities

Ramakrishnan Anand , Jarvis Charlotte , Thomas Jay , Armitage Suzanne , Lyons Greta , Halsall David , Chatterjee Krishna , Ramakrishnan Renuka

Introduction: Resistance to thyroid hormone beta, a rare disorder due to mutation in thyroid hormone receptor β, results in raised thyroid hormones with non-suppressed TSH and variable symptoms. Manifestations of RTHb in childhood include failure to thrive, propensity to ENT infections and behavioural abnormalities including ADHD. We report biochemical and behavioural responses to therapy with triiodothyroacetic acid (TRIAC), a centrally-acting thyroid ho...

hrp0098p2-4 | Adrenals and HPA Axis | ESPE2024

Pitfalls in diagnosis of Congenital Adrenal Hyperplasia due to 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency – A Problem of Assay Interference

Balagamage Chamila , Stirling Heather , Igbokwe Rebecca , Taylor David , Mohamed Zainaba , Idkowiak Jan

Introduction: 3-beta-hydroxysteroid dehydrogenase (HSD3B2) deficiency causes a rare form of Congenital Adrenal Hyperplasia (CAH) characterised by varying degrees of mineralocorticoid and glucocorticoid deficiencies with undermasculinisation in genetic males. The biochemical hallmarks are elevated androgen precursors in the delta5 pathway (dehydroepiandrosterone (DHEA) and 17-pregnenolone), with low mineralocorticoids and low (stimulated) cortisol levels. Immun...

hrp0095fc3.5 | Early Life and Multisystem Endocrinology | ESPE2022

Evaluating the Utility of Bi-functional Degrader Molecules for Selective Inhibition of PDE4 In Acrodysostosis Type2

Baillie George , Kyurkchieva Elka , Yan Sin Yuan , Ahmed Faisal , Rajapakse Navin , Schoolmeesters Angela , Richard Normand , Erdman Paul , Hecht David , Hoskote Chourasia Aparajita , Mercurio Frank , Fung Leah , Chan Kyle , Stirling David

Background: Acrodysostosis Type 2 (ACRDYS2) is a rare autosomal dominant skeletal dysplasia associated with intellectual disability and gain-of-function mutations in the phosphodiesterase type 4D gene (PDE4D) which, in turn, leads to a paucity of intracellular cAMP due to increased PDE4D activity. This increased PDE4 activity may be due to a greater existence of a mutant monomeric form of PDE4D. To date, the clinical use of PDE4 inhibitors in ACRDYS2 has been ...

hrp0097p1-253 | Fat, Metabolism and Obesity | ESPE2023

Effect of growth hormone on thermogenic and endocrine activity of brown adipose tissue and on the lipidome of children born small for gestational age

Murillo-Vallés Marta , González-López Lorena , Valls-Llussà Aina , González-Riaño Carolina , Cereijo-Tellez Rubén , Jimenez-Pavón David , Barbas Coral , Villarroya Francesc , Sánchez-Infantes David

Introduction: Brown adipose tissue (BAT) secretes molecules capable of modulating systemic metabolism. Growth hormone (GH) has hyperglycemic action, produces lipolysis and increases muscle mass. However, there are no human studies on its effect on the BAT and lipidome.Aim: To evaluate the effect of GH on BAT and lipidome in small for gestational age (SGA) patients and its relationship with adherence to treatment.<p c...

hrp0097p1-283 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2023

Developing a Collaborative Research Network to Accelerate the Understanding and Treatment of the Rare Disease Congenital Hyperinsulinism

Pasquini Pasquini Tai , Raskin Julie , De León-Crutchlow Diva , Banerjee Indi , Christesen Henrik , Conwell Louise , Dastamani Antonia , Flanagan Sarah , Gillis David , Kalish Jennifer , Lord Katherine , Stanley Charles , Zangen David , Thornton Paul

Background: Congenital Hyperinsulinism International (CHI) is an international non-profit organization focused on improving the lives of patients and families living with hyperinsulinism (HI). Despite many advances in the care of patients with HI, long term neurologic outcomes have not significantly improved, highlighting the need for CHI’s goals for robust and rapidly translatable research. We describe the development of a collaborative research network...

hrp0095fc11.3 | Late Breaking | ESPE2022

Dasiglucagon Significantly Reduces Requirement for Intravenous Glucose in Children with Congenital Hyperinsulinism ages 7 Days to 12 Months

De Leon Diva D. , Banerjee Indraneel , M Kendall David , Birch Sune , Bøge Eva , Ivkovic Jelena , Thornton Paul S

Background: Congenital hyperinsulinism (CHI) is a rare disease affecting neonates, infants, and children. CHI is characterized by dysregulated insulin secretion resulting in severe recurrent hypoglycemia. Early treatment is necessary to limit the risk of neurologic and developmental sequelae. Current treatment options are limited and inadequate. Dasiglucagon (DASI) is a glucagon analog suitable for continuous subcutaneous infusion which has been shown to raise...

hrp0095p1-179 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Loss of function of FIGNL1, a DNA damage response gene, is a novel cause of human ovarian dysgenesis

Florsheim Natan , Naugolny Larisa , Renbaum Paul , Lobel Orit , Y. Gold Merav , Goldberg Michal , Levy-Lahad Ephrat , Zangen David

Background: Severe Ovarian Dysgenesis (OD), a rare heterogeneous XX disorder of Sex Development presents clinically with primary amenorrhea, hypergonadotrophic hypogonadism and infertility. The genetic basis of OD remains unknown in 70% of cases. To identify novel causes of OD, we study patients in which known genes have been excluded.Methods: Whole-exome-sequencing was performed in a 14.5y old Ashkenazi Jewish, non-cons...

hrp0095p1-373 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

A novel Androgen Receptor mutation causes complete androgen receptor insensitivity syndrome with gender dysphoria and unusual postnatal androgen profile.

Cohen Amitay , Florsheim Nathan , Levy-Lahad Efrat , Eliyahu Mendelsohn Espen , Lavi Eran , Kerem Liya , Abu Libdeh Abdulsalam , Zangen David

Background: Androgen Insensitivity syndrome (AIS), the most common cause of XY DSD, is an X-linked recessive allelic disorder caused by Androgen Receptor (AR) gene mutations. The complete form (CAIS) stems from abrogation of AR activity and is characterized by an external female phenotype and scarce pubic hair, as well as lack of Mullerian structures. Postnatal gonadotropin and testosterone levels are not increased, and the classical ‘Mini-puberty’...

hrp0092rfc10.6 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

AA Mutation in the Nucleoporin-107 Gene Causes Aberrant Dpp/BMP Signaling and XX Gonadal Dysgenesis

Shorê Tikva , Levi^ Tgst , Kalifa Rachel , Rekler Dina , Dreifuss Amatzia , Weinberg-Shukron Ariella , Lavi Eran , Gerlitz Offer , Zangen David

Background: Though the genes and signalling pathways involved in sexual development have only been partially elucidated, it is known that their disruption can result in disorders of sexual development (DSD). XX ovarian dysgenesis (XX-OD) is a rare, genetically heterogeneous disorder characterized by underdeveloped and dysfunctional ovaries. We previously identified a novel missense mutation in Nucleoporin107 (Nup107, c.1339G>A, p.D447N), an essential compo...