Two children were born with ‘insatiable hunger’ that left them severely obese. Now scientists know why

Clinicians develop new therapy for children to eventually attain ‘near-normal weight’

Never-before-seen genetic mutations have been found in two children with a rare case of “insatiable hunger” that drove them to severe obesity.

The genetic mutations found in the children interfered with the hormone leptin, that tells the body when the stomach is full, said the research published in The New England Journal of Medicine.

The new discovery can shed more light on how hormones control weight gain. Previous studies have shown that the hormone – produced by the body’s white fat – interacts with the brainstem and brain’s hypothalamus region to control appetite.

It is also known to act as a signal that tells the body how much energy is stored as fat, depending on which it can switch a “starvation mode” on and off inside a person.

While previous research has revealed over a dozen genetic variations that interfered with leptin’s production, release or sensitivity in people – leading to insatiable hunger – the new case report reveals a completely different mechanism by which a mutation affecting the hormone causes severe obesity.

Two unrelated children, a 14-year-old boy and a two-year-old girl who had the different leptin-disrupting genetic mutations, were described by researchers, including those from the Ulm University Medical Center in Germany.

Both the children had high levels of leptin in their blood, coinciding with their high body fat percentages.

After ruling out other known mutations linked to leptin activity in the body, researchers found the kids carried distinct variants of the LEP gene.

The boy’s version was named P64S and the girl’s G59S, with each producing slightly different versions of the leptin hormone in their bodies.

In lab studies, scientists found that the leptin versions in the children’s bodies produced very weak signaling even though they had high quantities of the hormone.

“Both variants bind to the leptin receptor but trigger marginal, if any, signaling,” they wrote in the study.

Researchers said the leptin in the children could not carry the signal to their brains that their bodies had sufficient stored energy as fat, likely leading to their insatiety.

The children were then treated with a synthetic form of leptin, along with fasting and exercise programmes, to reduce their white fat and therefore, leptin production.

This approach “eventually evoked a therapeutic response, with a normalization of food intake and satiety and weight loss”, said researchers.

“Both patients eventually attained near-normal weight... No severe adverse events were observed,” scientists concluded in the study.