hrp0086fc5.4 | Management of Disorders of Insulin Secretion | ESPE2016

Persistent Beneficial Metabolic Effect after Five Years in a Cohort of 28 Subjects with Neonatal Diabetes owing to Potassium Channel Mutation and Transferred from Insulin to Sulfonylureas

Hoarau Marie , Fauret Anne-Laure , Busiah Kanetee , Godot Cecile , Colas Sandra , Treluyer Jean-Marc , Scharfmann Raphael , Cave Helene , Polak Michel , Beltrand Jacques

Background: Sulfonylureas (SU) have proven to be effective in patients with monogenic diabetes owing to potassium channel mutation. They allow the discontinuation of insulin and a good metabolic control. Long-term data arguing for a persistent beneficial effect of SU are missing.Objective and hypotheses: SU provide a good metabolic control maintained over time in patients with neonatal diabetes.Method: From a French cohort of 34 pa...

hrp0086rfc5.6 | Management of Disorders of Insulin Secretion | ESPE2016

Clinical Management of the Mitchell-Riley Syndrome Due to RFX6 Gene Mutations: Aggressive Support Results in Improved Outcome

Poidvin Amelie , Chandra Vikash , Fauret-Amsellem Anne-Laure , Cave Helene , Beltrand Jacques , Tubiana-Rufi Nadia , Carel Jean-Claude , Polak Michel , Scharfmann Raphael

Background: Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome associating neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis, duodenal atresia, and severe chronic diarrhea. Nine cases have been reported so far and the condition has a poor prognosis with five of nine patients died before the age of 6 months.Objective and hypotheses: To report on the clinical management and outcome of tw...

hrp0094p1-193 | Thyroid B | ESPE2021

Further evidence that Borealin/CDCA8 is involved in thyroid morphogenesis and aging

Didier-Mathon Hortense , Stoupa Athanasia , Karyiawasam Dulanjalee , Yde Sonny , Cagnard Nicolas , Nitschke Patrick , Scharfmann Raphael , Luton Dominique , Polak Michel , Carre Aurore ,

Background: We found BOREALIN/CDCA8 mutations in patients with Congenital Hypothyroidism and Thyroid Dysgenesis, varying from asymmetric lobes to athyreosis (Carré et al. Hum Mol Genet 2017). Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis. We demonstrated a new feature of BOREALIN: involvement in the adhesion and the migration of the thyrocytes.<strong...

hrp0086ha2 | BOREALIN Mutations in Thyroid Dysgenesis Reveal a New Function of this Protein in Cell Adhesion and Migration | ESPE2016

BOREALIN Mutations in Thyroid Dysgenesis Reveal a New Function of this Protein in Cell Adhesion and Migration

Carre Aurore , Stoupa Athanasia , Karyiawasam Dulanjalee , Gueriouz Manelle , Ramond Cyrille , Gaujoux Sebastien , Glaser Nicolas , Leger Juliane , Zenaty Delphine , Nitschke Patrick , Bole-Feysot Christine , Parisot Melanie , Hubert Laurence , Scharfmann Raphael , Munnich Arnold , Besmond Claude , Taylor William , Polak Michel

Background: Congenital hypothyroidism is primarily due to thyroid dysgenesis (TD). The genes implicated in TD, account for a small number of patients with monogenic forms, less than 5%. Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis.Objective and hypotheses: To understand the role of Borealin mutations found in patients with TD.Method: We performed whole exome sequencing (WES) ...

hrp0082fc9.6 | Beta cells | ESPE2014

Sulfonylurea Therapy Corrects Hypotonia, Attention Deficits, Improves Complex Neuropsychological Functions and Motricity in Patients with Neonatal Diabetes Secondary to Mutation in Potassium Channel Subunits, Through a CNS Effect

Beltrand Jacques , Vaivre-Douvret Laurence , Busiah Kanetee , Fournier Emmanuel , Boddaert Nathalie , Vera Myriam , Bahi-Buisson Nadia , Bui-Quoc Emmanuel , Ingster-Moati Isabelle , Flechtner Isabelle , Simon Albane , Scharfmann Raphael , Cave Helene , Elie Caroline , Polak Michel

Background: Sulfonylurea therapy (SU) allows a better metabolic control than insulin in patients with neonatal diabetes secondary to mutation in potassium channel subunits (ND-K). Most of these patients have neurological and neuromotor developmental impairments whose changes under SU has not been studied in a systematic and prospective way in a large cohort.Objective and Hypotheses: To demonstrate the beneficial effect of SU on neuropsychological functio...

hrp0089fc5.1 | Thyroid | ESPE2018

Beta1-Tubulin Gene (TUBB1) Mutations Cause Thyroid Dysgenesis Associated to Abnormal Platelet Morphology and Hyper-Aggregation

Carre Aurore , Stoupa Athanasia , Adam Frederic , Kariyawasam Dulanjalee , Strassel Catherine , Gawade Sanjay , Szinnai Gabor , Kauskot Alexandre , Lasne Dominique , Janke Carsten , Natarajan Kathiresan , Schmitt Alain , Bole-Feysot Christine , Nitschke Patrick , Leger Juliane , Jabot-Hanin Fabienne , Tores Frederic , Michel Anita , Munnich Arnold , Besmond Claude , Scharfmann Raphael , Lanza Francois , Borgel Delphine , Polak Michel , Federation Parisienne pour le Depistage et la Prevention des Handicaps de l'Enfant FPDPHE Michel

Background: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, with an incidence of 1:3000 neonates, and one of the most frequent preventable causes of mental retardation worldwide. Most (65%) cases of primary permanent CH are due to thyroid dysgenesis (TD). However, a genetic cause is identified in less than 5% of CH due to DT.Methods: We performed WES (Whole Exome Sequencing) for siblings with childhood-onset TD and we analy...

hrp0082np2.1 | Regenerative Endocrinology | ESPE2014

Regenerative Medicine for β Cell Replacement

Scharfmann R

Pancreatic β cells develop from endodermal pancreatic progenitors that first proliferate and next differentiate into functional insulin-producing cells. This developmental process is complex, each step being controlled by yet unknown signals. Theoretically, the development of a functional β cell mass can be enhanced by: i) activating the proliferation of pancreatic progenitors; ii) activating their differentiation into β cells; iii) activating the proliferation ...

hrp0086wg2.5 | ESPE Obesity Working Group (OWG) | ESPE2016

Palatability Can Drive Feeding Independent of AgRP Neurons

Raphael G.P.

Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical due to the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic, agouti-related protein-secreting neurons (AgRP neurons) represent primary orexigenic drives of homeostatic fe...

hrp0082p2-d1-369 | Fat Metabolism &amp; Obesity | ESPE2014

The Expression of IGF Type 1 Receptor is Increased in Obese Children

Ricco Rafaela , Custodio Rodrigo , Atique Patricia , Liberatore Raphael , Ricco Rubens , Martinelli Carlos

Background: Obese children are often taller than non-obese ones before puberty. Reports on the GH/IGF system in obese children are not consistent and do not explain the increased height observed. Changes in IGF1 bioavailability/bioactivity have been claimed as a possible explanation, however, no data is available regarding the expression of the IGF type 1 receptor (IGF1R) gene.Objective and hypotheses: To study the expression of IGF1R gene in obese child...

hrp0082p2-d1-585 | Thyroid | ESPE2014

Subclinical Hypothyroidism is Associated with Low IGF1 Levels and Decreased Growth Velocity

Bellini Helena , Maciel Lea , Custodio Rodrigo , Milani Soraia , Paula Mariana , Antonini Sonir , Liberatore Raphael , Martinelli Carlos

Background: Subclinical hypothyroidism (SH) is defined as normal tyrosine levels in the presence of TSH concentrations between 5 and 10 mU/ml. The impact of SH on IGF system and growth of infants remains unknown.Objective and hypotheses: To evaluate IGF1, IGFBP3 levels and growth velocity (GV) of infants with SH.Method: 98 children up to 36 months of age, recalled due to a TSH >5 mU/ml in the neonatal screening test, were divid...