Severe childhood obesity linked to genetic disorder

A UK RESEARCH team headed by a Dublin professor has, for the first time, linked severe childhood obesity to a genetic disorder. The findings, by Prof Stephen O'Rahilly, Dr Sadaf Farooqi and colleagues at Cambridge University, could quickly lead to new treatments for those suffering from the rare disease. It will also prompt new genetic studies which may discover other genetic causes for obesity.

The work involved a study of two young cousins, explained Prof O'Rahilly, a professor of metabolic medicine. Although of normal weight at birth, within months both children gained weight much too quickly. The girl, now eight, weighs almost 14st and the two-year-old boy weighs 4st 8lb.

Both were found to have a genetic defect causing an inability to produce a substance called leptin. Leptin is produced by fat cells and keeps the brain informed about fat", said Prof O'Rahilly, a UCD medical graduate. It controls appetite and the rate at which calories are burnt off.

He said the defects were similar to genetic defects found in mice in studies in 1994. The Cambridge research provided the "first proof" of leptin's importance in controlling human weight.

Mice with low leptin levels were found to eat more, burn less energy and put on weight. When treated with synthetic leptin, these abnormalities were reversed, according to the Cambridge research report, to be published tomorrow in the journal, No tore.

"The fact that we find the mutation in both cousins and not in their siblings is proof that there is a genetic cause for the disease," Prof O'Rahilly told The Irish Times. "We may be able to treat this by giving leptin."

This severe form of childhood obesity is very rare, but the work will lead to further studies of "how leptin works", explained the paper's joint primary author, Dr Farooqi. The focus, she said, would be on the places in the body where leptin has its effects, such as the brain.

Another genetic defect has already been identified by the Cambridge team and will be published in a report in Nature Genetics next month. In this case, a 40-year-old woman had a mutation in a gene which helps the body process insulin and other hormones, some of which have been linked to weight control. Her childhood obesity has been associated with this gene.

Prof O'Rahilly believes genes may play a large but as yet undefined part in obesity. It is worth noting, however, that very few overweight people have a leptin problem and so a single genetic defect is highly unlikely to be the cause of obesity for most.

"Your propensity to become obese is set by birth, but whether you do or not is more likely determined by environment," Prof O'Rahilly said.