Projectile vomiting in newborns: the gene hunt

Around one in 300 newborn babies needs life-saving surgery to stop projectile vomiting. No-one knows which babies will suffer until symptoms develop, threatening their lives with alarming speed. Researchers plan to identify the genes involved, with the ultimate aim of finding ways to avoid surgery and diagnose babies before they become ill.

What's the problem and who does it affect?

Babies face surgery by just 6 weeks' old

Each year in the UK, around 1000 babies with a condition called pyloric stenosis must have an urgent operation under general anaesthetic.

Babies with pyloric stenosis seem healthy at birth. But, by the tender age of just 3 to 6 weeks' old, their life is put in danger by severe vomiting and dehydration. This quickly becomes so bad that the babies can't keep any milk down. Without surgery, they would soon die.

Most operations are successful, though some babies suffer complications such as infected wounds.

A knowledge gap limits how doctors can help

Doctors know relatively little about pyloric stenosis, apart from the fact that the exit from the baby's stomach becomes blocked by abnormally thickened muscle.

No-one can predict which babies will develop the condition, even though it seems to run in families. Doctors can't make a diagnosis until babies are already poorly, and they rely on a surgical treatment that was first introduced in 1911.

What is the project trying to achieve?

Tracking down the gene

The researchers aim to find the faulty gene, or genes, that cause pyloric stenosis. They have already identified 768 people, from 145 families affected by the condition, who have agreed to take part in research studies.

Firstly, the team will study the genetic material - the DNA - both of people who had surgery for pyloric stenosis and of other members of their family. They hope to find out where the faulty gene is located, by looking for a region of DNA that is shared by all the people who suffered from pyloric stenosis.

Next, they will use on-line databases to find out which genes in this region of DNA are involved in the activity of stomach muscle, because babies with pyloric stenosis have overgrown muscle tissue in the wall of their stomach. By analyzing those genes, they hope to identify the faulty gene that causes the disease.

What are the researchers' credentials?

The research team has long been committed to studying pyloric stenosis. Drawing on well-established collaborations with leading paediatric hospitals, they plan to collect DNA samples from more than 400 families by the end of 2005. They know of no other researchers, neither in the UK nor abroad, who are gathering samples on such a large scale.

The combination of their expert knowledge of pyloric stenosis, technical skills, well-equipped laboratory and the patient dataset that they are assembling places them in a unique position to conduct a rigorous scientific investigation into the molecular genetics of pyloric stenosis.

Who stands to benefit from this research and how?

Filling the knowledge gap

Identifying the genes that cause pyloric stenosis, or that put babies at high risk of developing the condition, would be an exciting breakthrough. Initially, it would help explain what causes pyloric stenosis at a molecular level.

Towards avoiding illness and surgery

In the longer term, doctors' increased knowledge should lead to new ways to diagnose, treat and even prevent pyloric stenosis.

The researchers hope to enable doctors to diagnose the illness well before babies become ill. This should be possible because faulty genes act as markers of disease. So the researchers plan to devise a DNA-based screening test for pyloric stenosis. Then no-one need wait until babies suffer from projectile vomiting to diagnose the condition.

This project may also open the door to new treatments, preferably ones that mean babies escape surgery. Since surgery on newborns requires specialist staff and dedicated hospital facilities, a non-surgical treatment would also save the NHS a substantial amount of money.