Portal de Periódicos da CAPES

Congenital Leptin Deficiency Due to Homozygosity for the Δ133G Mutation: Report of Another Case and Evaluation of Response to Four Years of Leptin Therapy

2004; Oxford University Press; Volume: 89; Issue: 10 Linguagem: Inglês

10.1210/jc.2004-0376

1945-7197

William T. Gibson, I. Sadaf Farooqi, Mary Moreau, Alex M. DePaoli, Elizabeth Lawrence, Stephen O’Rahilly, Rebecca Trussell,

Adipokines, Inflammation, and Metabolic Diseases

Congenital leptin deficiency is a rare, but treatable, cause of severe early-onset obesity. To date, two United Kingdom families of Pakistani origin carrying a frameshift/premature stop mutation, c.398delG (Δ133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg105Trp), have been described. Affected subjects are homozygotes and manifest severe obesity and hyperphagia accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of recombinant leptin therapy have been reported in three children with the Δ133G mutation, and in all cases this has led to a dramatic resolution of clinical and biochemical abnormalities. We now report a Canadian child, of Pakistani origin but unrelated to the previously reported subjects, presenting with severe hyperphagia and obesity, who was found to be homozygous for the Δ133G mutation. In this child, 4 yr of therapy with sc injections of recombinant leptin provided additional evidence for the sustained beneficial effects of leptin replacement on fat mass, hyperinsulinemia, and hyperlipidemia. In addition, leptin administration corrected abnormal thyroid biochemistry and allowed the withdrawal of T4 treatment, providing additional support for the role of leptin in the regulation of the human hypothalamic-pituitary-thyroid axis.