Endocrine Abstracts

JOINT2056

Background: Childhood and adolescent obesity is increasing, and childhood obesity often persists into adulthood. The causes of obesity are complex, involving environmental, social, and genetic factors. Genetric factors are estimated to contribute between 40% and 75%. Both polygenic and monogenic obesity are influenced by genetic predisposition and environmental factors. Monogenic obesity frequently leads to severe obesity from early childhood and, although rare, recent advances have enabled treatment for genetic abnormalities in the leptin-melanocortin pathway. Identifying genetic causes can contribute to treatment, as well as aid in predicting future prognosis and genetic counseling.

Objective: The aim of this study is to identify the genetic causes of pediatric patients with severe obesity in a single institution in Japan and to contribute to future treatment.

Methods: We enrolled 14 pediatric patients with pediatric severe obesity (BMI percentile ≥120). Genetic panel testing for monogenic obesity was performed.

Results: The variants identified in unrelated 5 cases included 4 in GHRL and 1 in PCSK1.

Conclusion: Monogenic obesity is rare, however, in this cohort, variants were identified in 35.7% of children with severe obesity. Identifying genetic variation in obesity-related genes may provide insights into personalized therapeutic approaches, particularly for cases linked to the leptin-melanocortin pathway. A patient with PCSK1 variant in this cohort may be eligible for treatment with setmelanotide in the future if it becomes covered by insurance in Japan.