Bardet-Biedl Syndrome (BBS)
Disease State Overview
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive condition resulting in a gene mutation affecting the immotile cilia of cells. These immotile cilia are involved in cellular communication required for normal health and development. When these cilia are dysfunctional, a varying degree of BBS symptoms may present. Currently, cilia dysfunction cannot explain all the symptoms associated with BBS, however, BBS genes have a critical role in the MC4R pathway which regulates hunger. Disruption to the MC4R pathway in BBS leads to hyperphagia, a key symptom associated with obesity in BBS.
POMC, PCSK1 and LEPR Deficiency Obesities
Disease State Overview
Pro-opiomelanocortin (POMC), (PCSK1), and leptin receptor (LEPR) deficiency obesities are all 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.
PCSK1 Deficiency
PCSK1 deficiency is a rare form of genetic early-onset obesity. The PCSK1 gene, encodes a prohormone, PC1/3, that is involved in the regulation of food ingestion, and managing glucose and energy expenditures. A partial or total absence of PC1/3 activity may contribute to obesity.
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.