ESPE Abstracts

Background: Congenital leptin deficiency (CLD) is an extremely rare condition due to homozygous pathogenic mutations in the leptin (LEP) gene. The clinical manifestation of patients with CLD is severe early-onset obesity and hyperphagia. Most patients with pathogenic homozygous leptin gene mutations have low or undetectable leptin levels, whereas few cases show high bio-inactive circulating leptin levels. To date, around 20 variants in the LEP gene have been d...

Herein, we report the case of a 15-year-old Indian boy who initially presented for short stature and obesity. Based on in-depth clinical assessment, the pediatric endocrinology team conducted investigations along with genetic tests. Clinical investigations revealed parathyroid adenoma, pituitary macroadenoma (prolactinoma), and pancreatic neuroendocrine tumor adenoma. The phenotype was directing us towards the MEN syndromes, apart from polydactyly which is atypical for MEN syn...

Background: Monogenic obesity (MO) is a rare form of obesity caused by mutations in a single gene, and characterized by being severe and with early onset. The leptin-melanocortin pathway is the main pathway controlling satiety and food intake. Genetic variants in this pathway have been implicated in MO with many being identified in consanguineous populations. Another group of neuronal proteins important in the development of neuronal circuits linked to energy ...

Background: Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) is a nutrient-sensing protein that suppresses the RAS–RAF–MEK pathway and is known to have a role in glucose uptake and glycolysis. The expression of DYRK1B increases during adipogenic differentiation suggesting an important role in adipogenesis. Mutations in DYRK1B have been described in three Iranian families and five Caucasian patients w...

Background: Monogenic early onset obesity is mainly due to pathogenic mutations in a single gene involved in the leptin melanocortin signaling pathway. This pathway is essential for satiety and energy homeostasis. Adenylate cyclase 3 (ADCY3) is a transmembrane protein localized in the primary cilia of neurons and plays a vital role in converting ATP to cAMP, a secondary messenger that regulates various downstream signaling pathways that control carbohydrates a...

Background: Obesity is highly prevalent worldwide, particularly in the MENA region. Whilst simple obesity has a variable genetic and environmental basis, syndromic and non-syndromic monogenic obesity has a strong genetic component. Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury.Methods: Five children...

Context: Monogenic obesity (MO) is a rare form of obesity due to pathogenic variants in genes implicated in the leptin-melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the MC4R and Leptin genes are the commonest causes of MO. Determining the genetic causes has important clinical benefits as novel therapeutic interventions were developed for some forms of MO.Objective:<...

Background: Obesity is highly prevalent in the MENA region, especially in children and it has been associated with neurodegeneration. We have undertaken corneal confocal microscopy (CCM) to assess for evidence of neurodegeneration in children with simple obesity and monogenic obesity (MC4R gene mutation) and further assessed the effect of glucagon-like peptide 1 agonist (GLP-1) therapy on corneal nerve regeneration.Methods:</stro...