hrp0092fc11.3 | Pituitary, Neuroendocrinology and Puberty Session 2 | ESPE2019

A Novel Genetic Aetiology for Familial Neonatal Central Diabetes Insipidus

lavi Eran , Sharaf Muna , Abu-Libdeh Abdulsalam , Renbaum Pinchas , Levy-Lahad Ephrat , Zangen David

Background: Central diabetes insipidus (CDI) in the neonatal age is usually a result of intracranial insult, either congenital or acquired. Familial CDI is usually an autosomal dominant disorder, presenting later in childhood (1-6 y) with polyuria and mostly caused by mutations in the Neurophysin II moiety of the AVP-NPII prohormone gene; these interfere with prohormone processing leading to gradual destruction of AVP secreting cells and result in arginine vas...

hrp0094p1-184 | Pituitary B | ESPE2021

The pituitary gonadal axis is not responsive to GnRH administration in PCSK 1 dysfunction

Mendelsohn Espen Eliyahu , Lavi Eran , Cahn Ranit , Sharaf Muna , Abu Libdeh Abdulsalam , Zangen David ,

Introduction: Patients homozygous for mutation in the PCSK-1 gene present clinically with severe congenital diarrhea and variable hormonal defects due to lack of enzyme/prohormone processing by Prohormone Convertase 1/3 (PC1/3). Although absence of spontaneous puberty has been reported in patients with PCSK-1 mutations, no peptide hormone(s) in the hypothalamus-pituitary-gonadal axis (HPG) have been reported to be dependent on PC1/3 cleavage. Here we studied t...

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...

hrp0086rfc6.8 | Syndromes: Mechanisms and Management | ESPE2016

The Actual Incidence of Small for Gestational Age (SGA) Newborns and their Catch-up Growth is Dramatically Lower than Previously Considered

Lavi Eran , Shafrir Asher , Libdeh Abdulsalam Abu , Stein-Zamir Chen , Friedman Smadar Eventov , shoob Hanna , Zangen David Haim

Background: SGA is defined as birth weight under 2 standard deviations (SD) from the mean. Previous studies indicate that 10% of SGA babies do not have “catch-up growth” (CUG). They are eligible for growth hormone (GH) therapy to increase final height. The unexpected low demand for GH therapy in SGA babies, triggered us to survey the actual incidence of SGA and failure in CUG.Objective and hypotheses: To find the actual incidence of SGA and fai...

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...

hrp0092p1-128 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

The Novel Founder Homozygous V225M Mutation in the 17HSDB3 Gene Causes Aberrant Splicing and Severe XY-DSD

Levy-Khademi Floris , Zeligson Sharon , Klopstock Tehila , Chertin Boris , Avnon-Ziv Carmit , Renbaum Paul , Lavi Eran , Sharaf Muna , Perlman Shira , Behar Doron , Zahade Fouad , Levy-Lahad Ephrat , Zangen David , Segel Reeval

Background: Mutations in the gene HSD17B3 encoding the 17-beta hydroxysteroid dehydrogenase 3 enzyme cause testosterone insufficiency leading to XY DSD. In this study the clinical characteristics and molecular etiology of 3 new severe XY DSD cases from consanguineous families are elucidated.Clinical report: Three female patients (2 sisters and a single unrelated female) presented at ages 0.1, 8 and 0.7 years with ambiguo...

hrp0089pl6 | Personalized treatments using gut microbiome and clinical data | ESPE2018

Personalizing Treatments Using Microbiome and Clinical Data

Segal Eran

Accumulating evidence supports a causal role for the human gut microbiome in obesity, diabetes, metabolic disorders, cardiovascular disease, and numerous other conditions. I will present our research on the role of the human microbiome in health and disease, ultimately aimed at developing personalized medicine approaches that combine human genetics, microbiome, and nutrition. In one project, we tackled the subject of personalization of human nutrition, using a cohort of over 1...

hrp0092rfc5.5 | Thyroid | ESPE2019

A Novel Mutation in the Thyroglobulin Gene Leading to Neonatal Goiter and Congenital Hypothyroidism in an Eritrean Infant

Stern Eve , Kassif Eran , Schoenmakers Nadia , Gruber Noah , Pinhas-Hamiel Orit , Yeshayahu Yonatan

Background: Congenital hypothyroidism is a common condition with reported incidence between 1/2000 – 1/4000 live births. In approximately 85% of cases this is sporadic due to a structural abnormality of the thyroid gland. Approximately 15% of cases are hereditary and secondary to thyroid dyshormonogenesis. Most of these are due to mutations in one of the genes involved in iodine transport or organification, mutations in the thyroglobulin gene or d...