Pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity are both categorized as ultra-rare genetic disorders of obesity. Each disorder is the result of mutations in genes that are involved in hunger regulation. Due to this mutation, early-onset obesity is a hallmark of both disorders.
POMC Deficiency
The POMC gene typically writes the instructions for the melanocortin-4 receptor (MC4R) pathway. This pathway is involved with signaling the brain when we are hungry and when we are full. When there is a mutation present, this pathway is disrupted and the message of being full is no longer communicated to the brain, therefore resulting in the feeling of insatiable hunger.
LEPR Deficiency
The LEPR gene typically provides instructions for the leptin receptor. Leptin is a hormone that is made by the body’s fat cells. This hormone is involved in telling our brain that enough fat is being stored, and that we don’t need to eat anymore. When there is a mutation in the LEPR gene, the leptin does not form correctly and prevents leptin from sending that signal. Due to this message not being sent, the body believes that it is starving.