Case Study: an Obese Toddler with Mutant Leptin

The role of the hormone leptin in promoting obesity is a growing area of research. In a case study from Germany reported in the New England Journal of Medicine, Martin Wabitsch, MD, PhD and colleagues report success in treating an obese toddler with recombinant human leptin.

The 2-year-old boy had a body mass index of 44.6 when his parents brought him for treatment. More than half his weight of 43.3 kg was in fat (23.1 kg).

That might have led treating physicians to assume he had a leptin deficiency. But tests showed that the child actually had high levels of leptin. The problem was that his leptin was biologically inactive.

They determined that he had mutant D100Y leptin. This mutant protein was unable to bind to his leptin receptors. Without access to the hunger-regulating hormone, the boy had an insatiable appetite resulting in his eating way too much and becoming fatter and fatter.

The doctors decided to treat him with the recombinant human leptin, known as metreleptin. After getting parental consent, they started the dosage at 0.03 mg of metreleptin per kilogram of lean body weight per day.

The treatment “resulted in a rapid change in eating behavior, a reduction in daily energy intake, and substantial weight loss as well as in metabolic and hormonal changes,” Wabitch wrote in the article.

Mutations leading to biologically inactive hormones, are rare, the authors said. They noted that the boy’s parents have normal weight but that they are first cousins, and that the boy's anomality was congenital.

The lesson for physicians treating sudden onset childhood obesity is that “circulating levels of the hormone that appear to be normal in relation to body-mass index and fat mass do not rule out disease-causing mutations in the gene encoding leptin and might obscure the correct diagnosis.”

With treatment, the boy’s weight dropped steadily and by the 18^th week of therapy his BMI was down to 34.2 and his weight to 35.0 kg.