Recent research has revealed genetic mechanisms that lead to rare disorders of obesity. In particular, studies suggest that several genetic defects affecting the melanocortin-4 (MC4) pathway—which plays an important role in regulating appetite and weight—leads to intense feelings of hunger and to obesity.
Advances in genetic studies have identified several diseases that are the result of genetic defects affecting the MC4 pathway, including POMC deficiency obesity and LEPR deficiency obesity. These two disorders generally are associated with very rapid weight gain in childhood that continues into adulthood, and extreme and unrelenting appetite. Other characteristics sometimes associated with these genetic disorders are red hair and light skin that burns but never tans.
POMC deficiency is characterized by voracious infant feeding, rapid weight gain, and severe obesity, often in early infancy, with patients demonstrating remarkable weight increases many standard deviations above the normal weight growth curves.
LEPR deficiency also causes hyperphagia (an unusual increase in appetite) and severe, early-onset obesity. LEPR deficiency can also be associated with mild alterations in immune function, delayed puberty and short stature.