Genome Sequencing In NICU Can Speed Diagnosis Of Rare Inherited Diseases : Shots - Health News Rapid genome decoding and analysis have made it possible to quickly diagnose some baffling rare diseases that make babies sick. Even when there's no cure, the information can help families cope.

Fast DNA Sequencing Can Offer Diagnostic Clues When Newborns Need Intensive Care

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In this week's All Tech Considered, we look at how gene sequencing is changing the way doctors treat babies.


SHAPIRO: The technology and research have come along so quickly that it is now possible to go from a blood sample to a complicated diagnosis in just a couple of days. Doctors who treat newborns in the intensive care unit are turning to genome sequencing to help them identify difficult illnesses. NPR science correspondent Richard Harris reports on some of the pioneering work.

RICHARD HARRIS, BYLINE: When Nathaly Sweeney launched her career as a pediatric heart specialist just a few years ago, she says it was a struggle to anticipate which babies would need emergency surgery or when.

NATHALY SWEENEY: We just didn't know whose heart was going to fail first. There was no rhyme or reason of who was coming to the intensive care unit over and over again versus the ones that were doing well.

HARRIS: Now, just a few years later, Dr. Sweeney has at her fingertips the results of the complete genome sequence of her sickest patients in just a couple of days.

SWEENEY: This went fast. This went really, really fast.

HARRIS: We meet in the neonatal intensive care unit of Rady Children's Hospital in San Diego. Their doctors can figure out what's wrong with about two-thirds of these newborns without a pricey test. The rest have been medical mysteries.

SWEENEY: We had patients that were lying here in the hospital for six, seven months, not doing very well. The physicians would refer them for rapid whole genome sequencing and were diagnosing with something we didn't even think of - maybe was the underpinning of what's going on with this child.

HARRIS: The lab at Rady's Institute for Genomic Medicine has now sequenced the genomes of more than a thousand newborns. The institute has three million-dollar gene-sequencing machines. On a recent afternoon, Luca Van der Kraan is tending to one of them.

LUCA VAN DER KRAAN: NovaSeq 2's been having some issues. It's two years old now, so they replaced some hardware.

HARRIS: She's setting it up for a cleaning cycle to put it back in service. The two others are standing by for DNA samples that are being prepared in an adjacent lab.

VAN DER KRAAN: Typically, we load the sequencers at night, and then they run overnight. Data comes off around, like, 11 a.m., noon the next day.

HARRIS: You heard that right. An entire genome is decoded in about 16 hours.

Kasia Ellsworth is one of the experts waiting at a nearby office to analyze the information. That task has shrunk from months to typically just four hours, thanks to increasingly sophisticated software.

UNIDENTIFIED PERSON: Grab a chair. Maybe it'll be easier.

HARRIS: Ellsworth inputs a baby's symptoms into the software, which then spits out a long list of genetic variants that might be related to the illness.

KASIA ELLSWORTH: Then I'm looking through a list of those variants and then basically deciding whether or not something will be truly contributing to the disease or not.

HARRIS: About 40% of the time, a gene stands out, giving doctors a tentative diagnosis.

ELLSWORTH: You always feel very relieved, very happy and excited. But at the same time, you know, you kind of need to put it in perspective, you know? What does it mean for the family, for the patient, for the clinician, as well?

STEPHEN KINGSMORE: We now are at the point where the evidence is overwhelming that a rapid genome sequence can save a child's life.

HARRIS: Dr. Stephen Kingsmore, the institute's director, is the driving force behind this revolution. He says the information is only sometimes actionable.

KINGSMORE: About 1 in 4, it changes management. And about 1 in 5, we have a change in outcome.

HARRIS: A small share of these rare diseases actually have treatments. Otherwise, the information can help parents and doctors understand what's wrong with their baby, even if there is no treatment, or learn if death is inevitable.

KINGSMORE: And there, it's a very different conversation where we help guide parents through picking an appropriate point at which to say, enough is enough.

HARRIS: Of course, the hospital highlights the happier outcomes. One of Kingsmore's favorite examples is a bouncy girl named Sebastiana. He showed off her case recently in front of the Global Genes conference, a meeting of families with genetic conditions.


KINGSMORE: Sebastiana is sitting back there. There she is.


HARRIS: Sebastiana will be 3 years old in December.


KINGSMORE: She was critically ill in our intensive care unit. And in a couple of days, we gave the doctors the answer - it's Ohtahara syndrome. It comes with this specific therapy, and she hasn't had a seizure in 2 1/2 years. She doesn't take any medication.


HARRIS: Sounds miraculous, but when you meet Sebastiana and her mother Dolores Sebastian, a more complicated story emerges. Dolores vividly recalls the story of Sebastiana's difficult first day of life.

DOLORES SEBASTIAN: She was acting weird and screaming and crying and turning purple, and we weren't sure why.

HARRIS: The hospital where she was born rushed her to the neonatal intensive care unit across town at Rady. The baby was having frequent seizures. The following days were a nightmare for Dolores and her husband.

SEBASTIAN: It was - can't even describe it. I always keep on saying that, you know, at that moment, I was kind of, like, dead, but I was walking.

HARRIS: The hospital ran a battery of tests to look for severe brain damage. They couldn't get to the bottom of it.

SEBASTIAN: They came in and offered us the genomic testing, and they never told us, you know, how quick it would be.

HARRIS: She was surprised when the results were back in four days. The doctor told her they had identified a gene variant that can trigger seizures, as well as do other harm to the brain.

SEBASTIAN: And he said, this is how we're going to go ahead and change her medications now and treat her.

HARRIS: And did that make a difference?

SEBASTIAN: Huge difference, amazing difference - 'cause she was on a medication that was helping control her seizures, but she was sedated.

HARRIS: On the new medication, she was alert and able to eat without a feeding tube, her seizures under control. Dolores Sebastian says her daughter is, in fact, still taking that drug.

Controlling her seizures isn't a cure. Children who have this genetic variant can have anything from benign to debilitating symptoms. Sebastiana falls somewhere in between. For example, she has only a few words in her vocabulary as she approaches the age of 3.

SEBASTIAN: She took her first step when she was 2 years old - her first steps. So she's delayed in some things, but she's catching up very quickly. So she has PT. We're going to soon start speech therapy. She gets a lot of help, but everything's working.

HARRIS: Her genetic variant is the most common link to epilepsy, and it could've been diagnosed with a less expensive test, but that would've taken longer and wouldn't have cast as wide a net. Rady has now got the price of a whole genome sequence down to about $10,000, Kingsmore says. That's about the cost of one day in the intensive care unit.

KINGSMORE: In some babies, we avoid them being in the intensive care unit literally for months.

HARRIS: Most insurance companies and state Medicaid programs are still balking at the cost, but Kingsmore says private donors are helping support this effort in his hospital and at more than a dozen others scattered from Honolulu to Miami.

KINGSMORE: And that number grows every month.

HARRIS: Those hospitals send their samples to Rady for analysis. Kingsmore hopes that over the next three years, he can expand the service to reach 10,000 babies and several hundred children's hospitals. But he knows that getting diagnoses for these sick babies, often with rare diseases, is not enough.

KINGSMORE: We want to solve the next bottleneck, which is, I don't have a great treatment for this baby. It's going to be an incredibly exciting time in pediatrics.

HARRIS: Richard Harris, NPR News.

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