hrp0089rfc2.6 | Bone, Growth Plate & Mineral Metabolism 1 | ESPE2018

The Novel R211Q POP1 Homozygous Mutation Causes Severe Short Stature But Uniquely Only Subtle Skeletal Dysplasia

Abdulhadi-Atwan Maha , Klopshtock Tehila , Sharaf Muna , Weinberg-Shokrun Ariella , Levy-Lahad Ephrat , Zangen David

Background: Processing of Precursor 1 (POP1) is a core protein component of the Ribonuclease-Mitochondrial RNA Processing (RNase-MRP) enzymatic complex, an essential complex in all eukaryotes. Mutations in RMRP, encoding the RNA moiety of the complex cause cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders, characterized by severe disproportionate short stature. Recently, five patients harboring mutations in POP1 have been report...

hrp0086rfc9.1 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Neonatal Diabetes due to NKX2.2 Mutation – Genotype, Clinical Phenotype and Therapeutic Challenges in a Very Low Birth Weight Diabetic Neonate

Auerbach Adi , Shlomai Noa Ofek , Shokrun Ariella Weinberg , Levy-Lahad Ephrat , Zangen David

Background: Insulin treatment in a very low birth weight neonate having persistent hyperglycemia is challenging. The very recently reported novel human genetic cause of neonatal diabetes due to NKX2.2 pancreatic transcription factor mutations is associated with very low birth weight deliveries.Objective and hypotheses: To study the diagnostic process, the molecular genetics, the clinical phenotype, and the significant therapeutic challenges in the manage...

hrp0084p1-9 | Adrenal | ESPE2015

Founder Effect and the Clinical and Molecular Characteristics in a Cohort of Classical and Non-Classical Congenital Lipoid Adrenal Hyperplasia Due To StAR Mutations

Abu-Libdeh Abdulsalam , Shokrun Ariella Weinberg , Levy-Lahad Ephrat , Admoni Osnat , Tenenbaum-Rakover Yardena , Zangen David

Background: Classical and non-classical congenital lipoid adrenal hyperplasia (CLAH) are extremely rare condition caused by mutations in StAR. The degree of enzyme activity impairment determines the clinical phenotypes.Objective and hypotheses: To identify the genetic cause of primary adrenal insufficiency in a cohort of patients from 13 unrelated families with classical and non-classical CLAH, to correlate genotype to phenotype and to identify ...

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...

hrp0089p3-p019 | Adrenals and HPA Axis P3 | ESPE2018

Erythrocytosis as First Manifestation of Adrenal Mass

Valenzise Mariella , Cannavo Laura , Zirilli Giuseppina , Iaria Graziella , Lima Mario

Background: Erythrocytosis is characterized by increased number of red blood cells. Primary form is also known as polycythemia vera, while secondary forms can be due to several causes, among which hyperandrogenism. Although the association of severe hyperandrogenism and polyglobulia is known, literature data concerning this comorbidity are overall scanty, and completely lacking in pediatric age.Case report: We report the history of a 14 years-old girl ad...

hrp0082p2-d2-550 | Puberty and Neuroendocrinology (1) | ESPE2014

Final Height in a Boy with McCune–Albright Syndrome and Precocious Puberty Treated with Ketoconazole, Cyproterone Acetate, and Leuprolide Acetate Depot for More than 5 Years

Messina Maria Francesca , Aversa Tommaso , Valenzise Mariella , De Luca Filippo

Background: McCune–Albright syndrome (MAS) is a sporadic and rare disorder, clinically defined by the classic triad of cafè-au-lait skin lesions, polyostotic fibrous dysplasia, and peripheral precocious puberty. Precocious puberty is common in girls, but has been reported in only 15% of affected boys. Clinical trials on therapeutic management of precocious puberty in MAS boys are limited to case reports or small patient cohorts and no data are reported about final he...