ESPE Abstracts

Background: Early-onset severe obesity due to leptin deficiency typically results from a defect of leptin production or secretion due to mutations in the leptin gene. Recently we described a new form of leptin deficiency caused by bioinactivity of the hormone and associated with high circulating leptin levels (New England Journal of Medicine 2015 372 48–54).Method: Serum leptin was measured by ELISA. The leptin gene was seq...

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) is dramatically increasing among children worldwide. The gold standard for diagnosis is the liver biopsy. Reliable serum markers are lacking. Recently, circulating miRNAs have been studied as biomarkers of disease progression. Specifically, miR-122 was proposed as predictive marker for liver disease in adults, while no data are available for children.Objective and hypotheses: To inves...

Introduction: Monogenic obesity refers to a group of rare, early-onset forms of obesity and accounts for about 7% of patients with severe pediatric obesity. Recent reports demonstrate the emerging role of Src-homology-2 (SH2) B adaptor protein 1 (Sh2b1), an important component in the leptin-melanocortin pathway, as a key regulator of leptin and insulin signaling, with possible roles in the pathogenesis of obesity and diabetes. SH2B1 deletions are found to be a...

Background: Patients with rare monogenic obesity caused by biallelic variants of genes such as proopiomelanocortin (POMC; including variants in PCSK1) or leptin receptor (LEPR) deficiency, experience hyperphagia (a pathologic, insatiable hunger) and early-onset, severe obesity. This suggests potential increased risk over time of obesity-related comorbidities, including metabolic syndrome, a cluster of conditions associated with increased risk of cardiovascular...

Introduction: The soluble leptin receptor (sLR) is the main binding protein of leptin in the serum. It reflects the amount of membrane-bound leptin receptors (LEPR) as the sLR is produced by proteolytic cleavage of the extracellular domain of membrane-bound LEPR. Low sLR but high leptin levels were measured in patients with severe obesity. In patients with monogenic obesity caused by biallelic LEPR variants, sLR levels were found to be either undetect...

Background: Current reference values for leptin in childhood and adolescence are presented separately for girls and boys, and as a function of age without considering the variability of fat mass. This complicates the interpretation of measured serum leptin concentrations since fat mass is the major determinant of circulating leptin concentrations. To fill this gap, we aimed at pooling existing data (age, BMI, sex, tanner stage (TS), serum leptin concentrations...

Background: Disorders of sex development (DSD) are often due to disruption of the genetic programs that regulate gonad development. Some genes have been identified in these developmental pathways such as DAX-1, SOX-9, GATA-4 and others. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation. Congenital heart disease (CHD) and...

Introduction: As of May 2021, German law protects children with differences of sex development (DSD), including females with congenital adrenal hyperplasia (CAH), from non-consensual genital surgery. Parents can consent only in emergencies; all other surgeries require the child's consent. Exceptions are allowed by law, with the approval of the family court following a positive decision by a multidisciplinary committee. If the family presents a positive de...

Background: Obesity is increasingly being diagnosed in the paediatric population. Obesity during childhood and adolescents is related to an increased risk for cardiovascular diseases, high blood pressure, diabetes mellitus and menstrual disorders including heavy menstrual bleeding, oligomenorrhea, dysmenorrhea. The study aim: is to investigate the incidence of menstrual disorders in adolescents with severe obesity. <...

Background: Kinase suppressor of Ras 2 (KSR2) gene codes for a scaffold protein modulating intracellular pathways that involve MEK/BRAF cascade and AMPK signaling. KSR2 plays an important role in energy balance regulation, and KSR2 mutations were reported to be associated with obesity and insulin resistance in mice and humans. In transfected cells, several KSR2 mutations lead to impaired fatty acid oxidation, which improved under met...