Obesity due to leptin receptor (LEPR) deficiency

Obesity due to leptin receptor (LEPR) deficiency is an ultra-rare, monogenic neuroendocrine disorder caused by biallelic loss-of-function variants in the *LEPR* gene Clinically, affected individuals present with rapid, early-onset severe obesity driven by persistent hyperphagia that manifests within the first months of life despite normal birth weight The condition primarily impacts the neuroendocrine and metabolic systems and is frequently accompanied by endocrine abnormalities, including hypog...

Obesity due to leptin receptor (LEPR) deficiency is an ultra-rare, monogenic neuroendocrine disorder caused by biallelic loss-of-function variants in the *LEPR* gene The condition primarily impacts the neuroendocrine and metabolic systems and is frequently accompanied by endocrine abnormalities, including hypogonadotropic hypogonadism leading to pubertal failure and infertility

This defect impairs hypothalamic leptin-melanocortin signaling, disrupting satiety perception and energy expenditure Clinically, affected individuals present with rapid, early-onset severe obesity driven by persistent hyperphagia that manifests within the first months of life despite normal birth weight

This defect impairs hypothalamic leptin-melanocortin signaling, disrupting satiety perception and energy expenditure