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Meghana Keshavan, STAT
Meghana Keshavan, STAT
SAN DIEGO — When babies become intensely ill, it can be difficult to know what has gone wrong. But the answer, quite often, is hidden somewhere in their genes.
Whole-genome sequencing — in which scientists can read the nearly 3 billion chemical letters in DNA — can help turn up that answer. And scientists, increasingly, are laying out a case for using that tool in an intensive care setting, despite the upfront costs.
The data, they say, show over and over that early diagnosis of genetic disorders not only saves lives, but can keep long-term health care costs down.“Whole genome sequencing in the NICU is a no-brainer,” said Lucy Raymond, a professor of medical genetics and neurodevelopment at the University of Cambridge.
The field’s still in its nascency, and only a handful of hospitals offer whole-genome sequencing for babies — typically those who are among the sickest. As costs for genetic analysis become less prohibitive, however, an increasing number of hospitals are showing an interest in offering comprehensive testing.
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The need is real: Dr. David Dimmock, senior medical director of the Genomics Institute at Rady Children’s Hospital in San Diego, estimates that 1 in 4 children in level 4 NICUs — the units that can offer the most complex level of care — have an unrecognized genetic disorder. That translates to about 40,000 infants hospitalized in the U.S. each year, sickened by something going haywire in their genes.
Scientists at Rady’s have probed the complete genomes of nearly 500 critically ill babies in the past few years. The hospital partnered with San Diego sequencing giant Illumina back in 2015 to churn out rapid results, offering a full genomic analysis in four days, on average — and in as fast as 37 hours.
Speaking at this week’s conference of the American Society of Human Genetics in San Diego, Shareef Nahas, a senior director of the Rady’s project, said that a genetic disorder was ascertained in 163 of the 487 infants studied — about one-third. The results allowed doctors to change their treatment protocol for 117 of the families, about 77 percent. Rady’s estimates the program has ultimately saved it about $3 million on treatments that would have been unnecessary.
Whole-genome sequencing has been making the greatest impact in infants with neurological disease, Nahas said. In the study he did with his colleagues, 18 patients who came in with seizures were tested. Eight carried genes linked to epileptic encephalopathy, so they were treated accordingly.
Congenital heart disease is another area that could benefit tremendously from whole-genome sequencing, Nahas said. These are costly conditions, with more than $1.9 billion spent each year in the U.S. to mitigate their symptoms.
Nahas detailed one case in which a 5-week-old was brought to the hospital, breathing rapidly and turning blue. Scientists at Rady’s sequenced his genome. They found two pathogenic genes that interfered with certain metabolic pathways, leading to respiratory and heart failure.
“Most patients survive less than six months with this condition; the majority are diagnosed postmortem,” Nahas said. The baby is doing well today.
Whole-genome sequencing is typically reserved for young patients whose physicians already suspect a genetic disorder. By the time the symptoms are severe enough to indicate a genetic condition, however, it may be too late to offer an effective therapy.
At the University of Cambridge, Raymond and her team sequenced the genomes of 145 sick children. Most notably, she found that there wasn’t much correlation between genotype and phenotype — meaning that doctors conducting standardized testing would have no reason to suspect a specific genetic disorder. When babies are very young, they may be hospitalized for being ill, but the form of illness won’t necessarily fit the existing diagnostic criteria for the rare disease they have, she said. In her study, only 13 percent of the children showed symptoms that correlated with their eventual genetic diagnosis.
Without whole-genome sequencing in the NICU, she said, most of these genetic disorders might only be diagnosed later in life, when they’re far more challenging to treat.
Other hospitals are anxious to begin similar programs, though issues of scalability are a serious concern. Genome sequencing costs have come down, to be sure, but who will pay for these analyses? And will hospitals be equipped to carry out the necessary testing?
Rady’s work is currently supported through philanthropy and grants — insurers have yet to cover whole genome sequencing in a neonatal setting.
With a $2 million grant from the state of California, Rady’s is trying to explore how to scale whole-genome sequencing for infants in a new initiative dubbed “Project Baby Bear.” It’s also working with Medi-Cal, the state’s health care program for about 6 million children from low-income families. The project aims to diagnose another 100 critically — and inexplicably — ill infants admitted to the NICU unit using whole-genome sequencing.
“From there, we’ll go back to the state, show them the economic and clinical utility,” Nahas said. “We hope that they’ll like what they see, and approve reimbursement for whole genome sequencing in the NICU.”
This article is reproduced with permission from STAT. It was first published on Oct. 19, 2018. Find the original story here.
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