Early-Onset Obesity Caused by Monogenic Disorders

Purpose of Review: Obesity is a common problem encountered daily by pediatricians. Although most obesity results from an “obesogenic” environment, single gene mutations in the hypothalamic leptin-melanocortin pathway may cause severe hyperphagia and early-onset obesity. This review discusses features of monogenic obesity to help pediatricians identify affected patients and offers insights into diagnosis and treatment by pediatric endocrinologists, geneticists, and other subspecialists. Recent Findings: In addition to leptin, the leptin receptor, pro-opiomelanocortin (POMC), and the melanocortin receptors, genes mutated in children with monogenic obesity include single-minded 1, brain-derived neurotrophic factor, and tropomyosin receptor kinase B. Improved understanding of signaling pathways has stimulated the development of novel therapies, including recombinant leptin (metreleptin) for leptin deficiency and a melanocortin-4 receptor agonist (RM-493) for POMC deficiency, leptin receptor deficiency, and potentially prohormone convertase 1/3 deficiency. Summary: The recognition of monogenic obesity disorders is vital for genetic counseling and appropriate follow-up and treatment.

Duke Scholars

Author Laura Caitlin Page Pediatrics, Endocrinology

Author Michael Scott Freemark Pediatrics, Endocrinology