Mya Burkhart was only six months old when she went into cardiac arrest. Fortunately, she was in the hospital when it happened, brought there by her parents because she had trouble breathing. It was her eighth or ninth visit to the emergency room for her respiratory problems, but each time the doctors had sent the Burkharts home with more questions than answers.
Mya wasn’t developing at the normal rate. She couldn’t lift her head and wasn’t responding to people and things around her. Doctors thought she might have a muscle disorder, but her other symptoms did not fit with that diagnosis.
After her heart scare, Mya spent three weeks, including her first Christmas, in the ICU on a ventilator. “I couldn’t pick her up or anything,” says her mother Holly. Still unable to solve the mystery of what was ailing her, the doctors finally suggested she have her genome tested. Maybe, they hoped, her DNA would offer some clues about why she wasn’t growing normally.
Holly knew the test was still in the research stages, and that there was a chance that even it might not yield any more answers about her daughter’s condition. “At that point, I just wanted to try anything to find out what was wrong with her,” she says. It boiled down to balancing a chance that their baby would live or die.
Genetic screening, especially whole-genome screening in which people can learn about their possible risk for certain diseases, remains controversial, since the information is neither definitive nor always accurate. In most cases, genes can only predict, with a limited amount of certainty, whether a disease such as breast cancer or Alzheimer’s looms in a person’s future. As the Food and Drug Administration (FDA) contemplates the merits and efficacy of such screening, some doctors and researchers are using it with great success, according to a new study published in the journal Science Translational Medicine.
Researchers at Children’s Mercy Hospital in Kansas City, where Mya was treated, say that for 100 families, including the Burkharts, with children affected by either unknown disorders or brain abnormalities, genome screening helped 45% receive a new diagnosis, and guided 55% to a different treatment for their child’s disorder. Of the 100 families, 85 had been going from doctor to doctor in search of a diagnosis for an average of six and a half years.
“I was surprised by how many cases we found where a specific intervention can make a difference,” says Sarah Soden from the Center for Pediatric Genomic Medicine at Children’s Mercy and the study’s lead author. “For me it’s compelling enough to push the envelope and get younger kids diagnosed.”
In Mya’s case, her genome revealed a mutation in a gene responsible for transporting citrate; without it, her cells could not get the energy they needed. So far, only 13 babies have been confirmed with the condition, and all died before their first birthday after having seizures and respiratory infections. Once the genetic analysis revealed the deficiency, however, Mya was started on citrate supplements. She’s now 18 months old, having already lived nearly twice as long as the other confirmed cases. She has some developmental delays but she has not had any seizures and managed to avoid getting any serious respiratory infections.
Their success at Children’s Mercy are encouraging Soden and the study’s senior author, Dr. Stephen Kingsmore, to push ahead and determine how such screening can benefit more babies. About 5% of the 4 million babies born in the U.S. each year are admitted to the neonatal intensive care unit (NICU), and between those who are born with a genetic disorder and those who may have adverse drug interactions, he and his team anticipate that about 30%, or 60,000, may benefit from the personalized screening they offer.
For now, he and his team are targeting babies like Mya who are sick almost from the minute they enter the world, with symptoms and abnormalities that doctors simply cannot explain. For them, the screening can save families from uncertainty as well as the financial burden of having many different experts perform many different tests looking for a diagnosis. The average genetic sequencing for newborns costs around $5,000, but the average cost of a night’s stay in the Neonatal Intensive Care Unit (NICU) hovers around $8,000, and most babies spend days, if not weeks, in the units awaiting a diagnosis.
Kingsmore received a $1.5 million grant from the NIH to expand the screening program to other institutes, and he has reached out to hospitals in Florida, at the University of Maryland and in Oklahoma City to test the strategy in more babies. “If we can decrease the length of stay in the NICU it could certainly lead to huge potential cost savings,” says Dr. Alan Shuldiner, associate dean of personalized medicine at the University of Maryland.
In the latest study, Soden says that on average, families spent more than $30,000 on genetic testing alone to figure out what was ailing their babies; those who had their genomes screened paid about $3,000 for an answer.
The key to Kingsmore’s success is a system that starts with a doctor punching in a newborn’s baffling symptoms and ends with a genetic readout. The “magic juice,” as he calls it, is a database of 10,000 symptoms that typically affect infants, from simple coughs and fevers and enlarged hearts to all manner of abnormal lab readings. The baby’s unique combination of these symptoms is mapped onto the 3,000 genes that experts have so far connected to about 4,000 diseases. “No physician on the planet earth could carry that database around in his head,” says Kingsmore. But that’s what desperate parents, whose babies’ lives are at stake, expect them to do. So Kingsmore’s program accomplishes the feat, spitting out, in rank order, a list of potential genetic diagnoses. That targeted tally of diseases then directs doctors to focus on a much more manageable list of 10 or, at the most, 50 genes (from a possible 20,000 or so) that could be mutated and responsible for the baby’s condition.
While there is no argument that such testing can save lives, the more challenging question is who should be tested, and when. There is also still debate among those in the genetics and medical communities about how to interpret genomic data. “Some people would argue that he is still reporting his experimental findings, and moving too soon from the research arena into the clinical arena,” says Dr. Edward McCabe, chief medical officer of the March of Dimes.
Ethicists are concerned about the coerciveness inherent in any hand extended to parents whose babies would otherwise die; no matter how carefully and comprehensively doctors word their request, parents in that situation may not fully process the risks and benefits and be unable to provide a truly informed consent. What if the baby falls into the minority for whom the testing doesn’t yield a diagnosis or treatment? When faced with inevitable death on the one hand, and a chance, however, small, of avoiding that death on the other, can there ever really be a choice?
The stakes are especially high since in some cases, the disorders won’t lead to established and approved treatments, but experimental ones without known risks and benefits. But as the value of such testing becomes more obvious, more centers may consider sequencing more newborns’ genes. “These babies, because they are brand new, are salvageable,” says Kingsmore. “Many patients we see with genetic illnesses already have ravaged organs. In contrast, with newborn babies we have the opportunity to halt a disease early in its progression,” he says.
“I think this testing is definitely something that everybody should consider,” Holly Burkhart says. “Without it, we probably never would have figured out what was wrong with Mya. We probably would be in the same place we were a few months ago.” Instead, Mya is now smiling at her mom and making progress. “The testing helped us find answers, and tell us where we need to go from here,” she says.