Fast genome tests are diagnosing some of the sickest babies in time to save them

Rylee Supple seemed like a perfectly healthy baby when she was born in August 2016. But after a few months, her parents, Amy Jaeger and Robert Supple, realized something wasn’t right: instead of making normal baby movements, like kicking and grasping, Rylee’s body would shake and spasm.

Jaeger and Supple were worried. They took Rylee to a doctor for a slew of tests, which all came back negative. And in the following months, Rylee got even worse. She couldn’t raise her head or sit up like other babies her age, and she began sweating profusely.

Increasingly concerned, her parents took her to see neurologist Jennifer Friedman at Rady Children’s Hospital San Diego. She suggested trying a wider-ranging medical test called whole-genome sequencing, a technique that spells out the complete order of a person’s DNA—all six billion genetic letters—and looks for abnormalities to help figure out what’s wrong.

Usually it takes weeks for scientists to sequence an entire genome. But Friedman and her colleagues at Rady have sped up the process to less than a week, making it much faster to identify what’s wrong with critically ill babies so they can get the treatment they need to recover.

Genetic diseases are the leading cause of death for infants in North America, affecting an estimated 4 percent of newborns. So while the work at Rady is still in the research stage, costing the hospital about $6,000 per baby, the hope is that it could lead to a standard medical test with the potential to save thousands of lives.

Friedman ordered the test for Rylee on a Tuesday last August; at Rady’s in-house lab, technicians extracted DNA from the toddler’s blood and began sequencing it. By the following Tuesday, the lab had delivered a diagnosis: a rare, inherited neurological condition called infantile Parkinsonism. A type of movement disorder, it can be fatal if left untreated.

A few days after her parents learned the diagnosis, Rylee started a medication called levodopa.

“Almost immediately we started seeing dramatic changes,” Supple says. Now, Rylee’s shaking is under control. She can sit up on her own and, at 18 months old, is learning how to crawl.

Since Rylee was sequenced, Rady’s lab has gotten even faster. The turnaround time for a whole genome sequence can be as short as four days.

“This is part of a new wave of precision medicine,” says Stephen Kingsmore, president and CEO of Rady Children’s Institute for Genomic Medicine. By learning the genetics behind a baby’s symptoms, doctors gain a better idea of what drugs may or may not work and could end up saving a baby’s life.

In order to get Rylee and other babies the help they need as quickly as possible, technicians at Rady have modified and combined existing sequencing technologies to make the process faster. First they insert snippets of DNA into small glass slides, which are scanned with a laser in a sequencing machine. The machine reads the DNA letters so that the genetic code can be reassembled and analyzed on a computer. Then lab workers use a data-crunching computer chip and a combination of different software tools to spot genetic mutations and identify the cause of illness.

So far, researchers at Rady have used their rapid technique to sequence the genomes of 340 children, most of them newborns and infants. It turned up a diagnosis in about a third of those babies, and within that group, the results led doctors to change the course of treatment for about two-thirds. Sometimes that meant avoiding medications or procedures that would have been harmful to the child. In many cases, those changes helped the baby get well faster and leave the hospital sooner; sometimes it saved the baby’s life, Kingsmore says. 

Anastasia Wise, an epidemiologist with the National Human Genome Research Institute, part of the National Institutes of Health, says this means of speeding genome sequencing could make the technique a more practical option in situations where patients have severe and life-threatening illnesses that need to be treated quickly.

And Rady researchers are getting even faster. In February, Kingsmore and his team broke the speed record for sequencing a human genome, doing it in 19.5 hours (consider that the first human genome took 13 years to sequence, from 1990 to 2003).

Kingsmore and his team wanted to get the time down so it would fit into a physician’s shift in the intensive care unit, which can last 24 hours or more. That way, the same doctor who ordered the test could see the results, he says.

For now, 19.5-hour sequencing won’t be the norm. Kingsmore and his team had help from a few genomics companies, including Illumina; they’ll need to further refine the process before using it for future cases.

Rady is expanding its rapid sequencing efforts, though. Although it’s still in the research stage, it is now offering the test at four other children’s hospitals in Minnesota, Colorado, Florida, and California. Over the next few years, it hopes to sequence a total of 5,000 genomes using its rapid method.

Sometimes genome sequencing reveals a condition that isn’t treatable, or the baby dies while in the ICU. Still, just knowing why a baby died can give some closure to these parents, Kingsmore says.

“Being able to put a name on it and being able meet up with other parents can help with the grieving process,” he says.