ESPE Abstracts

Objective: To present the spectrum of monogenic obesity presenting to a tertiary children’s hospital in UAE

Introduction: Monogenic obesity is increasingly recognized as a cause of severe early-onset obesity. Monogenic obesity syndromes arise from single gene mutations affecting critical for regulation of body weight and energy balance. Children with monogenic obesity often experience severe, early-onset weight gain, accompanied by relentless hunger and insatiable appetite. These mutations can affect various pathways, including leptin signaling, melanocortin signaling, and other mechanisms involved in appetite control and energy homeostasis. The development of new therapies for genetic obesity gives added importance to their identification.

Methodology: Retrospective analysis of 97 children who underwent testing for monogenic obesity since 2016.

Results: Seven out of 97 patients tested positive, while (as is common in our region) 28 had variants of unknown significance, of which 27 were considered to be consistent with the known phenotype. We classified the 34 positive and likely positive cases as Ciliopathies (n = 8), other syndromic cases (n = 5) or non-syndromic (n = 21); and further divided the non-syndromic cases into melanocortin pathway defects (n = 16) and others (n = 5).

Discussion: We present positive genetic findings in 34 of 97 cases investigated for monogenic obesity between 2016 and 2024. The most common causes were Melanocortin pathway defects followed by ciliopathies. Syndromic obesity (excluding ciliopathies) had a diverse range of genetic etiologies. Clinical manifestations of monogenic obesity in children extend beyond excessive weight gain and adiposity. These individuals may exhibit endocrinopathies, respiratory, renal and metabolic complications with significant impact their overall health and wellbeing. Moreover, the psychosocial implications of severe obesity at a young age can lead to stigmatization and compromised quality of life for affected children and their families. Early recognition of monogenic obesity is crucial to mitigate these detrimental effects and provide timely interventions including use of appropriate targeted genetic therapies (Setmelanotide, Leptin) where appropriate.