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 (Delta133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg(105)Trp), 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 Delta133G 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 Delta133G 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 T(4) treatment, providing additional support for the role of leptin in the regulation of the human hypothalamic-pituitary-thyroid axis.

Two methods of introducing obese adolescents to aerobic exercise were compared. A fast-start group began with five aerobic sessions per week and gradually reduced these to three over a period of 12 weeks. A slow-start group began with one per week and gradually increased to three. A control group had an equivalent amount of time in interactive group sessions and nonaerobic activity. The program was assessed by physical fitness, anthropometry, and attendance. Results were analyzed by multivariate analysis. The method of introducing exercise to the subjects produced no significant differences on measures of fitness or anthropometry. Significant effects for time were shown for strength, push-ups, body mass index, the sum of five skinfolds, gluteal and abdominal circumferences, weight, and percent overweight. Significant differences in the absenteeism rates were shown among groups. However, no relationship was found between absenteeism and changes in weight or overall fitness levels.

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