Congenital Leptin Receptor Deficiency Causes Child Obesity

Deficiency of receptor differs from deficiency in hormone itself

WEDNESDAY, Jan. 17 (HealthDay News) -- Congenital deficiency of the leptin receptor differs from a deficiency of leptin itself and is marked by excessive appetite in childhood and severe obesity without signs of developmental delay or dysmorphism, according to study findings published in the Jan. 18 issue of the New England Journal of Medicine.

I. Sadaf Farooqi, M.B., B.S., Ph.D., of Addenbrooke's Hospital in Cambridge, U.K., and colleagues sequenced the leptin-receptor gene in 300 subjects with hyperphagia and severe early-onset obesity. The cohort included 90 index patients from blood-related families.

Three percent of the 300 subjects had nonsense or missense leptin receptor mutations. The missense mutations resulted in impaired receptor signaling. Blood levels of leptin were not elevated among people with leptin-receptor deficiency. Less severe than leptin deficiency, leptin-receptor deficiency is characterized by hyperphagia, severe obesity, changes in immune function and delayed puberty, the researchers found.

"This diagnosis has implications for the care of these patients, both in terms of genetic counseling of the affected families and in terms of future prospects for treatment, since these patients would be predicted to have favorable response to drugs targeted at pathways downstream of the leptin receptor," the researchers conclude.

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