Rapid Sequencing Of Babies' Genes May Save Lives
The technology of rapid whole genome sequencing could help in finding mode of treatment faster and revolutionize health care for acutely sick infants.
Rapid Sequencing of genes offers early diagnosis of diseases in babies
- Rapid gene sequencing is much faster than regular gene tests
- Researchers say that rapid sequencing is cost effective
- Early and effective treatment is made possible through rapid sequencing
The answer: "We're doing everything we can."
"Everything" was about to have a new meaning. Two days later, Kara and Michael Coltrin were asked whether they were willing to have their baby participate in a study that would analyze their and Maverick's DNA to determine if there might be a genetic cause to the infant's distress. After the parents said yes, blood samples from the three were run through a powerful new genetic sequencer that can crunch all 3 billion base pairs from each person in record time and reveal the biology behind thousands of common and rare diseases.
Exactly 39 hours later, when he was 9 days old, they got a diagnosis: Maverick had a form of epilepsy that was treatable with vitamin B6 supplements. "I was in disbelief that all we had to do was give him a vitamin to stop his seizures," says Kara Coltrin.
The technology is called rapid whole genome sequencing, and doctors say it could revolutionize health care for acutely sick infants.
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"When you have newborn babies with unexplained diseases, many are dying or suffering permanent brain or organ damage," says Stephen Kingsmore, an internist who founded Rady's genomics institute in 2014. (In February, he set a Guinness world record for sequencing a genome in 19.5 hours.) "But if we can diagnose them rapidly, we can change those outcomes. If we had to wait four to six weeks with the standard genetic testing that's available nationwide, Maverick would be dead."
Kingsmore is trying to make the case that this technology should be standard care in every neonatal intensive care unit, or NICU, in the nation. As part of a $25 million federal project that funds newborn sequencing research, the Rady team published the results of a study comparing traditional and this newest method in 42 infants with suspected genetic disorders. Rapid sequencing offered diagnoses for 18 babies, while standard genetic tests identified a disease in only four cases. Most important, the information from the advanced technique helped doctors recommend lifesaving surgeries or medications for 11 of the infants.
In another trial that randomly assigned 65 infants to either standard genetic testing or rapid sequencing, the evidence for the latter was so compelling that the study was stopped midway. "If you as the investigator truly believe that one technology arm is superior to the other, then it may become unethical to still randomize and deprive half the patients from it," says Josh Petrikin, a neonatologist at Children's Mercy Kansas City and one of the lead authors of that shortened study.
As with many innovations, the technology is expensive and isn't covered by insurance. To set up a lab like the one at Rady would cost an estimated $15 million, says Kingsmore. A bill was introduced in Congress this year that encourages states to fund sequencing for certain sick children.
Researchers argue that rapid sequencing is cost-effective: The cases of six infants in the Rady study for whom quicker diagnoses changed their course of care resulted in hospitalization savings of $800,000, which justified the $675,000 price tag of performing rapid sequencing for all 42 families. "We did this study to show better outcomes for patients but also to show it's economically feasible," says study co-author Lauge Farnaes, a pediatric hematologist-oncologist at Rady. "It's a win-win."
Yet cost won't be the deciding factor for insurers, predicts Scott Grosse, who researches health economics at the Centers for Disease Control and Prevention. "Rapid whole genome sequencing is still considered investigational, and payers don't want anecdotal evidence," he says. "The bigger question is whether there's solid evidence that when the technology is applied in practice there's widespread benefit."
Grosse says that innovative technology isn't the driving force behind higher U.S. health-care costs. In a March JAMA commentary on why the United States spends twice as much on medical care as other wealthy nations, authors from the Harvard T.H. Chan School of Public Health blamed increased administrative costs, drug prices and physician salaries.
In addition to generating more research, doctors need to identify which patients will receive the most value, adds Kathryn Phillips, who studies health-care technology at the University of California at San Francisco. "It's unlikely we can help all babies with rapid sequencing," she says. In other words, not all patients are like Maverick, for whom rapid sequencing saved his life. For some patients, getting a diagnosis sooner won't change their course of treatment. Some babies have diseases that don't have treatments. Some babies are already terminal.
"Anytime you have a new technology, you have to determine who might benefit from a cheaper test," she says. For example, current testing methods include analyzing a single gene or panel of genes or DNA microarray that targets multiple regions in the genome.
Yet doctors say you can't put a dollar amount on the power of naming as fast as possible the monster that's harming a child. Not only does a diagnosis - even a diagnosis for which no treatment is available - provide psychological relief, it also stops babies from undergoing unnecessary testing. In the saddest cases, a fatal diagnosis might allow parents time to prepare for a death. "Sometimes an answer tells you there is no answer, and that can be helpful to families," says Petrikin.
Melissa Griffith of Dallas knows firsthand the pain of waiting to find out what was wrong with her daughter. After noticing that 18-month-old Ellis could no longer lift a spoon to feed herself, Griffith took her to several neurologists who spent four months unsuccessfully pursuing futile tests that could not explain her sudden severe muscle weakness. Eventually, one ran genetic tests on Ellis (using a version covered by insurance) and found that she had a genetic disorder treatable with massive doses of the vitamin riboflavin.
By then, though, Ellis's condition had worsened. "Ellis is slowly gaining back her strength, but I believe that if sequencing had been first line, she'd still be walking," says Griffith of her daughter who is now 3 1/2 years old. "She still can't use her upper body, but last week she shuffled across the house with her dad hovering over her." Griffith recently helped start the Cure RTD Foundation with two other families to raise money for research in hopes of speeding up her recovery.
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In the future, cost might be less of an issue, as the price of decoding a person's genome continues to drop. Today, it's about $1,000, compared with $300,000 in 2006, not including data analysis and interpretation. And in January of last year, Illumina, the market leader in DNA sequencers, introduced the NovaSeq machine, which company CEO Francis deSouza has said could one day bring the price for sequencing down to $100.
In February, Illumina announced a clinical trial at five sites to compare the health outcomes of acutely ill infants who receive whole genome sequencing results within 15 days of birth with those who get them after two months.
Kingsmore imagines a day when faster sequencing means a NICU doctor could order a DNA test, learn the results and prescribe a treatment all within a possible 24-hour shift. In the meantime, Rady has established partnerships with several children's hospitals across the country so doctors can ship a patient's blood overnight to San Diego for DNA analysis.
Part of getting the word out about a new technology, however, is communicating what life was like without it. "I recently decoded the DNA of a 16-year-old who had seizures when he was a baby. He's now in a pediatric nursing home with a long-term serious illness," says Kingsmore, adding that he could have treated the teenager with medication and a diet to control his blood sugar soon after birth. "If he'd been tested as a baby, we could have prevented this."
(This story has not been edited by NDTV staff and is auto-generated from a syndicated feed.)
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