hrp0089p2-p076 | Diabetes & Insulin P2 | ESPE2018

Novel Gata6-Mutation in a Boy with Neonatal Diabetes and Diaphragmatic Hernia

Gaisl Odile Christin , Konrad Daniel , Steindl Katharina , Lang-Muritano Mariarosaria

Background: Onset of diabetes in the neonatal period with additional malformations e.g. congenital heart defects should always be suspicious for an underlying genetic disorder. For example, GATA6-mutations were identified in children with congenital heart defects and neonatal diabetes. The latter may be due to pancreas agenesis. Herein we present a novel GATA6-mutation in a boy with transient neonatal diabetes, diaphragmatic hernia, congenital heart defect and early onset scol...

hrp0084p2-488 | Hypo | ESPE2015

Unexplained Altered States of Consciousness in a Girl

Graf Stefanie , Gerster Karine , Kroiss Sabine , Konrad Daniel , Schonle Eugen

Background: In children, congenital hyperinsulinism is the most common cause for endogenous hyperinsulinaemic hypoglycaemia (HH). Beyond infancy other diagnoses may be considered, such as insulinoma, an insulin-secreting neuroendocrine tumour (NET) arising mostly from the pancreas. The latter is a rare cause of HH in children. The estimated incidence of insulinoma is 1:250’000 person-years of all age groups with a median age at diagnosis of 47 years. Herein, we report an ...

hrp0092rfc10.5 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

VVariants in NWD1 Gene Leading to Different Degrees of Gonadal Dysgenesis

Aeppli Tim , Gaisl Odile , Sproll Patrick , Lang-Muritano Mariarosaria , Nef Serge , Konrad Daniel , Biason-Lauber Anna

Introduction: Mammalian sex development is directly dependent on gonadal determination. Whole exome sequencing in patients with differences of sex development (DSD) allows the discovery of new factors involved in human sex development. One of these factors is NWD1 (NACHT and WD repeat domain containing 1) a cytosolic protein that seems to play a role in modulating androgen receptor signaling. We identified variants in the NWD1 gene in six und...

hrp0092p2-271 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Follow-Up of Two Similar Patients with Steroidogenic Factor-1 (SF-1/ NR5A1) Variants, in Two Different Eras

Gaisl Odile , Aeppli Tim , Sproll Patrick , Lang-Muritano Mariarosaria , Nef Serge , Konrad Daniel , Biason-Lauber Anna

Abstract: Steroidogenic factor 1 (SF1)/"nuclear receptor subfamily 5 group A member 1" (NR5A1) is involved in adrenal and gonadal development, steroidogenesis and reproduction. The first patient, published in 1999 presented with a 46,XY difference of sex development (DSD) and adrenal insufficiency. The following year the first female patient with only adrenal insufficiency was described. Since then, heterozygous changes in SF-1/NR5A1 causing 46,XY DSD ...

hrp0089fc8.1 | Sex differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2018

Estrogen Receptor 2 Variant as a Novel Cause for Dysgenetic Ovaries

Lang-Muritano Mariarosaria , Sproll Patrick , Wyss Sascha , Kolly Anne , Hurlimann Renate , Konrad Daniel , Biason-Lauber Anna

Background: Variants in the estrogen receptor α (ESR1) have previously been described in male and female patients presenting with estrogen resistance. Estrogen resistance is characterized by delayed bone-age, early-onset osteoporosis, delayed puberty and multicystic ovaries in women. So far, no clinical consequences of variants in the estrogen receptor β (ESR2) have been reported in 46,XX patients, although ESR2 variants have previously been implicated in 46,XY DSD p...

hrp0086p2-p65 | Adrenal P2 | ESPE2016

A Novel Mutation of DAX-1 (NR0B1) in a Boy with X-linked Adrenal Hypoplasia Congenita

Gerster Karine , Katschnig Claudia , Wyss Sascha , Kolly Anne , Biason-Lauber Anna , Konrad Daniel

Background: DAX-1 (NR0B1) plays a key role in adrenal and reproductive development. It interacts with other nuclear receptors; however, its exact biological role remains unclear. In men most patients with X-linked adrenal hypoplasia congenita (AHC) present with acute adrenal failure. To date DAX-1 mutations have been found in more than 100 families or patients with X-linked AHC.Results: We report the case of a 2.5-year-old boy who presented with a histor...

hrp0089p2-p346 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P2 | ESPE2018

Current Medical Care of Children and Adolescents with Disorders/differences of Sex Development in Switzerland

Sommer Grit , Konrad Daniel , Kuhlmann Beatrice , l'Allemand Dagmar , Phan-Hug Franziska , Hauschild Michael , Schwitzgebel Valerie , Tonella Paolo , Hess Melanie , Zumsteg Urs , Lauber-Biason Anna , Flueck Christa E.

Introduction: Since 2000 understanding of biology of sex development increased tremendously thanks to genetic research. This lead to new classification for persons with disorders/differences of sex development (DSD) based on genetics, and guidelines from the UK recommend revising medical care for persons with DSD by setting up interdisciplinary DSD teams. In Switzerland, persons with DSD asked for better care, stimulating the Swiss National Ethics Commission in 2012 to recomme...

hrp0082p1-d3-17 | Adrenals & HP Axis (1) | ESPE2014

Aldosterone/Renin Ratio as Key Player in the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants

Ruecker Beate , Lang-Muritano Mariarosaria , Spanaus Katharina , Welzel Maik , Lallemand Dagmar , Phan-Hug Franziska , Konrad Daniel , Katschnig Claudia , Holterhus Paul-Martin , Schoenle Eugen

Background: Primary hypoaldosteronism (PA) is a rare inborn disorder with life-threatening symptoms in newborns and infants due to an aldosterone synthase defect. As plasma aldosterone concentration (PAC) can remain in the normal range, interpretation of the laboratory findings could be difficult and might lead to delayed initiation of therapy.Objective and Hypotheses: This study aims to show that PAC/PRC (plasma renin concentration) rat...

hrp0094p2-396 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2021

Combining big data science with clinics: Novel approach for understanding human sex development and its variants.

Rodriguez Gutierrez Daniel , Sproll Patrick , Von der Decken Isabel , Stevenson Brian , Lang-Muritano Mariarosaria , Konrad Daniel , L’Allemand Dagmar , Nef Serge , Biason-Lauber Anna ,

Background/Introduction: Whole exome sequencing (WES) revolutionized clinical genetics in patients with differences of sex development (DSD). However, our ability to interpret WES data is limited by our incomplete understanding of the mechanisms involved in DSD. Thus, we created a methodology that scores potential candidates based on single cells transcriptomics of human male gonadal cells and applied it to WES data from a cohort of genetically male (46,XY) DS...

hrp0094p2-453 | Thyroid | ESPE2021

Kinetics of FT4 serum concentrations in newborns and infants with congenital hypothyroidism during follow-up differ in the three severity groups

Steffens Britta , Gächter Pascal , Koch Gilbert , l'Allemand Dagmar , Janner Marco , Konrad Daniel , Welzel Tatjana , Pfister Marc , Szinnai Gabor

Background: The goal of congenital hypothyroidism (CH) treatment is rapid normalization and maintenance of TSH and FT4 in the reference range. Recommended starting dose of levothyroxine (LT4) ranges from 10-15 mg/kg/d. Hyperthyroxinemia can be accepted in the context of normal TSH and LT4 should only be reduced in case of symptoms or repeatedly increased FT4. The aim of this study was to quantify duration and maximum peak of FT4 levels outside the reference range for each CH s...