Thus, the aim of the present study was to: (1) determine the prevalence of carriers of damaging or unresolved MC4R mutations in a cohort of children and adolescents with overweight or obesity participating in a structured longitudinal lifestyle intervention at TCOC, (2) describe the clinical characteristics of carriers with obesity and compare them to noncarriers, and (3) assess differences in weight loss intervention response between carriers and noncarriers by analyzing changes in anthropometrics, body composition, and metabolic traits. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.