hrp0082s8.2 | Novel Therapies in Paediatric Endocrinology | ESPE2014

Treatment of Hypophosphatasia

Greenburg C

Hypophosphatasia (HPP), an inborn-error-of-metabolism, has broad-ranging severity caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). HPP in children features premature loss of deciduous teeth often with impaired skeletal mineralization, poor growth, static myopathy, and compromised physical function. To date there are no approved treatments for HPP. Perinatal and infantile forms have very high morbidity and mortality and the j...

hrp0092p2-251 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

3β-HSD2 Deficiency Due to Compound Heterozygosity of a Missense Mutation (p.Thr259Met) and a Frameshift Deletion (p.Lys273ArgFs*7) in an Under-Virilized Infant Male with Salt Wasting

Leka-Emiri Sofia , Taibi Ludmia , Fotinou Aspasia , Vlachopapadopoulou Elpis , Michalacos Stefanos , de Roux Nicolas

Objectives: To describe clinical, hormonal and genetic findings of an under-virilized infant male, 13 month old, of afghani origin, presented at the emergency department with salt-wasting adrenal crisis.Case report: The patient, a 13 month old male infant, presented at the emergency department with complaints of vomiting and fever. Physical examination was significant for severe dehydration along with perineal hypospadia...

hrp0089fc13.4 | Pituitary, Neuroendocrinology and Puberty 2 | ESPE2018

The Kallman Syndrome Gene Product is Specifically Expressed in ACTH-Expressing Cells and Dysplays Sexual Dimorphism Expression in Human Fetal Pituitary

Guimiot Fabien , Bonnard Adeline , Soussi-Yaniscostas Nadia , Schnoll Carol , de Roux Nicolas

Kallman syndrome is defined by the association of anosmia due to an agenesis of the olfactory bulbs and hypogonadotropic hypogonadism due to a GnRH deficiency which is currently explained by a deficit of GnRH neuron migration from the olfactory placode toward the hypothalamus. In fact, the X-linked form of KS is due to loss of function mutations in ANOS1 which encodes an extracellular protein (ANOSMIN) interacting with cell membrane heparin sulfate proteoglycans but a...

hrp0089p3-p043 | Bone, Growth Plate & Mineral Metabolism P3 | ESPE2018

Low Level of Vitamin D in Children Increases the Risk of Bone Fractures

Nicolas Georges , Hoyek Fady , Assaf Elias , Abi Fares Georges , Akiki Simon

Introduction: The physiological process by which vitamin D regulates calcium and phosphorus metabolism, the major mineral constituents of bone tissue, is by far very well understood. However, the clinical implementation of vitamin D deficiency on bone fragility in childhood remains controversial.Objective: The aim of this case-control study is to investigate the prevalence of vitamin D deficiency among Lebanese children who experienced a ‘low-energy...

hrp0089p2-p195 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

The Benefit of Universal Neonatal Screening for Hypoglycemia

Nicolas Georges , chaaban Riham , faddous-Khalifeh Marie-Claude , Souaiby Juliana , Salemeh Yara

Introduction: Hypoglycemia is a common problem in neonatal period associated with adverse neurological outcome and brain injury if treatment was not provided. AAP and PES recommended screening for hypoglycemia only in newborns with risk factors but many others neonates may present episodes of asymptomatic hypoglycemia without any known risk factor.Objectives: To assess the incidence of hypoglycemia in healthy full term neonates without any risk factors i...

hrp0086fc12.1 | Neuroendocrinology | ESPE2016

Rabconnectin3-α is Indispensable for the Activation and Maturation of the GnRH Neuronal Network

Tata Brooke , Harbulot Carole , Csaba Zsolt , Jacquier Sandrine , de Roux Nicolas

Background: Acquisition and maintenance of fertility in mammals rely on the function of Gonadotropin Releasing Hormone (GnRH) neurons. During the juvenile period, GnRH neurons undergo morphological maturation, which involves changes in synaptic inputs and neuropeptide activation from afferent neurons. The functional importance of this maturation could be a pre-requisite for puberty onset. However, the mechanisms behind these dynamic changes have yet to be identified.<p cla...

hrp0086rfc2.7 | Bone &amp; Mineral Metabolism | ESPE2016

Effect of Paternal Loss-of-Function Mutations of GNAS on Growth During the Childhood: A Role for XL

Tran Lea Chantal , Brehin Anne-Claire , Richard Nicolas , Kottler Marie-Laure

Background: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia when paternally inherited. Mutations on the paternal, but not the maternal, GNAS allele are associated with intrauterine growth retardation (IUGR). Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2–13 (including XL and Gαs) than with exo...

hrp0086rfc10.1 | Perinatal Endocrinology | ESPE2016

Paternal Loss-of-Function Mutations of GNAS and Growth Retardation in a Mice Model: A Specific Placental Transcriptomic Signature?

Tran Lea Chantal , Ballandone Celine , Vaiman Daniel , Barbaux Sandrine , Richard Nicolas , Kottler Marie-Laure

Background: GNAS gene is a complex imprinted locus, resulting in the expression of at least four transcripts (XL, NESP55, A/B and Gsα) characterized by their specific exon 1 and common exons 2-13. While Gαs is biallelically expressed in most tissues, XL is only expressed from the paternal allele. Maternally inherited, loss-of-function mutations affecting those GNAS exons that ...

hrp0086p1-p360 | Gonads &amp; DSD P1 | ESPE2016

A Novel Familial Androgen Receptor Mutation (W752G) in Complete Androgen Insensitivity Syndrome: Use of in vitro Study According to the Nature of Amino Acid Substitution

Paris Francoise , Gaspari Laura , Boulahtouf Abdel , Kalfa Nicolas , Sultan Charles , Balaguer Patrick

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development and are associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome) to milder degrees of undervirilization (partial and mild forms).Aims and objectives: To specify how a phenotype-genotype correlation can be refined by in vitro study based on the nature of amino acid substitutio...

hrp0082p1-d3-48 | Bone (1) | ESPE2014

Paternal Isodisomy and Sporadic Pseudohypoparathyroidism I-b

Colson Cindy , Brehin Anne Claire , Abeguile Genevieve , Decamp Matthieu , Richard Nicolas , Kottler Marie-Laure

Background: Patients affected by pseudohypoparathyroidism type 1b (PHPI-b) develop resistance to PTH leading to hypocalcemia and hyperphosphoremia, which is often associated with resistance to TSH. PHP-Ib is associated with methylation changes at one or several differentially methylated regions (DMRs) within the GNAS complex locus, located at 20q13.2–13.3. This locus gives rise to several different transcripts (NESP55, XL, A/B), with varying patterns of imprinted expressi...