ESPE2021 ePoster Category 1 Fat, Metabolism and Obesity B (10 abstracts)
Monogenic obesity in children: focusing on SH2B1 deletion
Eleni Z Giannopoulou 1 , Stefanie Zorn 1 , Melanie Schirmer 1 , Gloria Herrmann 1 , Sabine Heger 2 , Thomas Reinehr 3 , Christian Denzer 1 , Hannah Rabenstein 4 , Julia von Schnurbein 1 & Martin Wabitsch 1
1Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany; 2Department of Pediatric Endocrinology, Children’s Hospital Auf der Bult, Hannover, Germany; 3Department of Pediatric Endocrinology, Diabetes and Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten-Herdecke, Datteln, Germany; 4Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany
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 associated with obesity, insulin resistance, hyperphagia and developmental delay in humans; however, only a few children with SH2B1 deletions have been described so far.Methods: We describe the phenotype of n = 7 children (3 male; age range: 2.8 – 18.0 years) with heterozygous SH2B1 deletions and present their BMI trajectories from birth onwards. Screening for obesity-associated co-morbidities was performed for all children at time of genetic diagnosis. Results: All children with SH2B1 deletions had a normal BMI at birth but presented an extreme weight gain during the first 5 years of life. Hyperphagia was not a constant feature of the patients. A broad spectrum of neurodevelopmental abnormalities, including speech delay, learning difficulties, autistic traits, behavioural problems (aggressiveness) and attention deficit hyperactivity disorder was observed. In most cases developmental delay was the reason for genetic testing. Five patients presented with elevated fasting insulin levels, one patient developed diabetes mellitus type 2 at the age of 9 years, four patients had dyslipidemia and four developed non-alcoholic fatty liver disease at an early age. Discussion/Conclusion: SH2B1 deletions in children were found to be associated with severe, early-onset obesity and developmental delay. Obesity-associated co-morbidities appeared early in life. Early genetic diagnostic testing in suspicious patients and early screening for co-morbidities is recommended. New therapeutic approaches, including setmelanotide, a MC4R agonist, are currently available for children with SH2B1 deletions in the context of clinical trials.
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