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...

hrp0089p3-p125 | Fat, Metabolism and Obesity P3 | ESPE2018

NKX2-2 Human Mutation Causes Neonatal Diabetes followed by Severe Infantile Obesity Associated with Paradoxical Upregulated Ghrelin Levels – Do Beta-cells Secrete Ghrelin?

Auerbach Adi , Cohen Amitay , Lavi Eran , Abdulhaq Najwa , Shokrun Ariella Weinberg , Levy-Lahad Ephrat , Hemi Rina , David Zangen

Background: NKX2-2 gene mutation (reported in 3 cases worldwide) cause severe IUGR and neonatal diabetes. Beta-cells of the mice Nkx2-2 (−/−) model were recently shown to convert into cells producing the appetite-promoting peptide ghrelin. Classically, ghrelin secretion is stimulated during fast and suppressed by nutrients or glucose ingestion in all age groups. In obese children this ghrelin suppression reaches a minimum of 60% of base...

hrp0086p1-p349 | Gonads & DSD P1 | ESPE2016

Severe 5 Alpha Reductase 2 Deficiency with Aphallia is Caused by p.Y91H SRD5A2 Mutation and is Responsive to Dihydrotestosterone Administration During Childhood

Auerbach Adi , Weinberg Shokrun Ariella , Abdelhak Najwa , Lavi Eran , Hidas Guy , Landau Yehezkel , Levy-Lahad Ephrat , Zangen David

Background: 5-alpha-reductase-2 (5α-RD2) deficiency is an autosomal recessive 46,XY disorder of sexual development, characterized by undervirilized prepubertal males with ambiguous genitalia. The pubertal rise in testosterone and 5α-RD1 isoenzyme activity causes virilization, often resulting in gender assignment change. Early precise diagnosis which anticipate adult function is critical for treatment and gender assignment.Objective and hypothes...

hrp0082p1-d2-4 | Adrenals & HP Axis | ESPE2014

Mineralo and Glucocorticoid Deficiency in Early Infancy are Caused by a Founder Novel Mutation in the Nicotinamide Nucleotide Transhydrogenase Gene

Abu-Libdeh Abdulsalam , Weinberg-Shukron Ariella , Zeligson Sharon , Zhadeh Fouad , Carmel Liran , Renbaum Paul , Levy-Lahad Ephrat , Zangen David

Background: Nicotinamide nucleotide transhydrogenase (NNT) gene mutations have been recently shown to cause familial glucocorticoid deficiency (FGD), by decreasing reactive oxygen species (ROS) detoxification in adrenocortical cells. Affected infants present within the first few months with isolated glucocorticoid deficiency.Objective and Hypotheses: To study the genetic etiology of four cases presenting uniquely with neonatal addisonian crisis (both min...

hrp0086fc5.5 | Management of Disorders of Insulin Secretion | ESPE2016

DPP-4 Inhibitor is an Alternative Effective Treatment in a Common Cause of Anti-GAD Negative “Type 1 Diabetes” - A Founder CISD2 Mutation

Abdulhag Ulla Najwa , Weinberg-Shukron Ariella , Abdelhadi Maha Atwan , Leibovitz Gil , Levy-Lahad Ephrat , Aurbach Adi , Lavi Eran , Abassi Muntaser , Wilchansky Michael , Libdeh Abdelsalam Abu , Zangen David

Background: Wolfram syndrome type 2 (WFS2) characterized by childhood GI ulcers/ bleeding, diabetes, and neurodegeneration with optic atrophy and hearing loss was recently elucidated as caused by CISD2/NAF-1 gene mutation. NAF-1 suppression in cells results in intra-mitochondrial accumulation of iron, increased ROS generation and consequently increased cellular apoptosis. So far only two mutations in four families were reported.Objective: Elucidate the c...

hrp0098p1-305 | Late Breaking 2 | ESPE2024

Lipodystrophy severity score improves in patients with generalized lipodystrophy following metreleptin treatment

Brush Maiah , Tuska Becca , Brown Rebecca

Generalized lipodystrophy (GLD) is characterized by near total loss of subcutaneous fat, leading to low concentrations of leptin. Complications of GLD are heterogenous, including severe insulin resistance, diabetes, hypertriglyceridemia, pancreatitis, liver, kidney, and heart disease, and reproductive dysfunction. Leptin replacement therapy using metreleptin improves many of these metabolic abnormalities. A lipodystrophy severity score (LDS) has been developed to quantify dise...

hrp0098p3-328 | Late Breaking | ESPE2024

Temple syndrome; genetics and characteristics

Hashim Raihana , Tatton-Brown Katrina , Albanese Assunta

Background: Temple syndrome (TS14) is an imprinting disorder caused by maternal uniparental disomy of chromosome 14 (UPD(14)mat), paternal deletion of 14q32 or an isolated methylation defect of MEG3-DMR. TS14 is characterised by pre- and postnatal growth retardation, hypotonia and feeding difficulties, obesity during childhood and adolescence, short stature, and precocious puberty.Method: This is a comparison of phenotyp...

hrp0095p1-497 | GH and IGFs | ESPE2022

Metabolomics profile of children with growth hormone deficiency

Shilo Smadar , Bar Noam , Halloun Rana , Cohen Michal , Rossman Hagai , Gal Shoshana , Oren Meirav , Malitsky Sergey , Itkin Maxim , Shahaf Nir , Lotan-Pompan Maya , Godneva Anastasia , Weinberger Adina , Tiosano Dov , Segal Eran

Background and Objectives: In recent years, a growing number of studies investigated the profile of serum metabolomics in health and disease. These studies have led to the discovery of novel biological biomarkers and causative agents for a variety of medical conditions. Here, we focused on profiling serum metabolites of children diagnosed with growth hormone deficiency (GHD).Methods: We conducted a prospective study and ...

hrp0095p1-276 | Fat, Metabolism and Obesity | ESPE2022

Natural History of Pregnancy and Pregnancy Outcomes in Metreleptin-Treated vs Untreated Subjects with Lipodystrophy

Brite Brianna , Abel Brent , Cochran Elaine , Brown Rebecca

Metreleptin is a leptin analog used to treat metabolic complications of lipodystrophy, a set of rare disorders characterized by generalized (GL) or regional (PL) deficiency of adipose tissue, resulting in insulin resistance, diabetes, dyslipidemia, steatohepatitis, and reproductive dysfunction. Metreleptin increases fertility, particularly in GL; spontaneous pregnancy without metreleptin was reported in only 4 patients with GL. Risks of metreleptin suggested by rodent studies ...

hrp0084p3-1226 | Thyroid | ESPE2015

A Rare Adverse Effect of Radioactive Iodine Therapy in a Child with Graves’ Disease

Walsh Elizabeth , Brown Marcie Drury , Crudo David , Constantaocs Cathrine

Background: Radioactive iodine (RAI) therapy has become the preferred treatment for Graves’ disease in children. Its use has found favour due to the risk of adverse effects in medical management and the invasiveness of thyroidectomy. Side effects of RAI in adults are well-documented and include dry mouth, sore throat, and neck pain. With its relatively recent application to paediatric patients, there is not a complete understanding of adverse effects in the paediatric pop...