Critically ill babies in Australia have had their lives saved after their genomes were rapidly sequenced as part of a first-of-its-kind trial.
Some babies are born extremely sick: for example, they may have seizures or be unable to breathe on their own. It has traditionally been difficult to determine what causes their symptoms. In many cases, children have died or have had permanent disabilities due to missing out on a diagnosis and then not receiving the appropriate treatment.
To address this, a small number of hospitals worldwide have experimented with sequencing sick babies’ genomes to uncover if they have one of more than 7000 rare genetic conditions.
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On average, these studies diagnosed genetic conditions in around 37 per cent of critically ill infants, allowing them to receive more tailored medical care, at Rady Children’s Hospital-San Diego in California, said at the in Melbourne.
“These studies have been really successful, but they’ve tended to be limited to single children’s hospitals,” says at the Victorian Clinical Genetics Services in Australia.
Stark and her colleagues therefore launched an Australia-wide trial into whole-genome sequencing for critically ill infants.
The trial, which ran from 2018 to 2022, involved 450 babies and children at every children’s hospital in the country. Just over half of the participants were under 1 month old.
On average, it took 2.9 days and cost AUS$15,000 (US$10,000) per child to collect a blood sample, sequence their genome, analyse the results and return a report to their doctors.
River Weatherby in Sydney was one of the babies in the trial. “When he was first born and they put him on my chest, they noticed he wasn’t really breathing,” says his mother Cody. River was put on a machine to help him breathe, but he continued to get sicker. Tests showed he had an enlarged liver and spleen and low platelets, and he required several blood transfusions. At one point, Cody says doctors told her that River may not survive the night.
As part of the trial, River’s parents agreed to have his genome sequenced. The results showed he has a rare condition called Gaucher disease, caused by a faulty variant of a gene called GBA. This causes the build-up of fatty substances in the body, particularly in the liver and spleen, and can result in a life expectancy of less than 2 years in severe cases.
Following his diagnosis, River’s parents agreed to start him on an when he was 2 weeks old. Now, “he’s a typical 2-year-old boy, he’s very full of energy, just non-stop”, says Cody.
River was one of 240 trial participants who were diagnosed with a genetic condition. The remaining 210 may have genetic conditions that haven’t yet been characterised or may have been unwell due to a non-genetic cause, such as a bacterial infection, says Stark, who presented the trial results at the RCPA meeting on 24 February.
Of those who received a diagnosis, around 10 per cent then had effective treatments. This proportion is expected to increase as more treatments become available, says Stark. For example, five gene therapies – which replace faulty genes with functioning copies – have recently been approved in the US and many more are in trials.
The children who were diagnosed with genetic conditions that don’t yet have treatments still benefited, says Stark. “Having a specific diagnosis tends to improve overall medical care because it means you don’t have to have unnecessary investigations or see specialists who aren’t relevant,” she says. “It also avoids what we call the diagnostic odyssey, whereby families spend years just trying to get an answer.”
The participants for whom no genetic condition was identified also had better outcomes as a result of being in the trial. “Providing a negative result can help the clinical team direct their thinking away from certain diagnoses and sometimes give them the confidence to forgo invasive tests, such as lung or liver biopsies,” says Stark.
The diagnosis time of less than three days was key to the trial’s success, she says. A decade ago, sequencing a person’s genome typically took four to six weeks, she says. “For babies in intensive care, time is really of the essence.”
The swift turnaround also meant the trial saved the Australian health system an estimated AUS$25,000 per child on average by reducing the need for other expensive tests and shortening the time in intensive care.
Kingsmore told the RCPA meeting about a similar trial he oversaw at five children’s hospitals. It also ran rapid whole-genome sequencing on sick babies and produced net savings of around .
Stark and her colleagues are now seeking government funding to make such sequencing permanently available across Australia, not just as part of a trial. In October 2022, England’s National Health Service announced that it would .
Cody says that she and River’s father feel like the “luckiest parents ever” after their son took part in the trial. “River is living, breathing proof of how important early diagnosis can be,” she says.
