Thursday, January 16, 2014

(BN) Baby DNA Analysis Ushers in Brave New World of Treatment

(Bloomberg ) When Kira Walker was three weeks old, her pediatrician noticed a problem. She was frequently hungry and had dangerously low blood sugar for no obvious reason.

Kira was born in Kansas City, Missouri, where her doctors had access to a service few hospitals can match. Her DNA was sent to Children's Mercy Hospital geneticist Stephen Kingsmore, who is able to determine a diagnosis in a day or two for half the babies with mysterious diseases referred to him. Until recently, these riddles took years to solve, or were never unraveled at all.

Hundreds of babies across the U.S. are having massive portions of their DNA deciphered as part of a five-year, U.S.- funded project to understand and navigate the brave new world of infant genetic testing. Kingsmore and a handful of other scientists are taking gene sequencing to the next level, using the technology to design treatment for infants with rare and unusual illnesses, and in some cases, finding therapies for genetic abnormalities never seen before.

Related: Human Gene Mapping Price to Drop to $1,000, Illumina Says

"The big picture is that medicine will be transformed when the genome is part of our medical record," he said in an interview in his laboratory. "The art of medicine will move closer to becoming a science."

About 5 percent of all babies born in the U.S., some 200,000 a year, probably suffer from a rare disorder, said Michael Watson, executive director of the American College of Medical Genetics and Genomics in Bethesda, Maryland.

Promising Information

Infant genetic testing may succeed in shedding light on conditions such as progeria, the disease of premature aging that killed Sam Berns, a 17-year-old from Foxborough, Massachusetts who was the subject of a recent HBO documentary. Testing some babies might lead to more knowledge about the disease and perhaps enable early experimental treatment, Watson said.

Sequencing gives a readout of the genome, the instructions each of the body's cells carries for making and maintaining tissues. Genomes change from one generation to the next and certain alterations can result in diseases, some of them both rare and serious. That's why sequencing the genes of infants holds so much promise.

Still, many parents and doctors remain wary as health experts grapple with a myriad of issues: who will pay, how much of the information should be shared with families, and whether the procedure should only be used in sick babies. About a quarter of the parents with sick children who are eligible for free genome sequencing through his program decline it, Kingsmore said.

Dramatic Benefits

For those who go ahead, the benefits can be dramatic and swift. Kingsmore's program at Children's Mercy is among the most technologically advanced in the world. Using powerful sequencers from Illumina Inc., the biggest maker of DNA-decoders, he can sequence a child's entire genome in 24 hours for about $12,000, which includes interpreting the data. Just over a decade ago, the same process took 10 years and cost more than $2 billion. Once the results are ready it often takes no more than 10 minutes to find the mutation linked to the disease.

In July, Kira Walker began to appear increasingly hungry, and would often awaken to eat ravenously.

"She was starving all the time," her mother, Amanda Webb, recalled. "All she wanted to do was eat."

The girl turned out to have very low blood sugar, which is unusual in a young child, and can cause brain damage. Kira's doctor, Children's Mercy endocrinologist Mark Clements, gave her glucose through an intravenous tube and a drug to stop her from making insulin, the hormone that lowers blood sugar.

Kira's Genome

It didn't work. Her blood sugar levels remained alarmingly low, and she was frequently listless and unresponsive. Clements asked Kingsmore to sequence Kira's genome. The sample went to the Genome Center on a Friday evening, and by Sunday, Clements had an answer.

"It's incredible when you think of the years it took us to sequence the first human genome and now we can do it in a weekend," Clements said.

What Kingsmore found was highly unusual. Kira had inherited a gene mutation from her father that spurs activity in the islet cells that make insulin. However, in an unusual twist, only a portion of her cells had the mutation.

That meant that Kira's doctors could take out part of her pancreas, rather than the entire gland, an operation that would have rendered her diabetic. With half a pancreas, she continues to make insulin, and at six months of age, her blood sugars are now normal.

"It was such a relief," her mother said. "It was very tense for a while there, and we had little idea of what was going on."

Improving Survival

Kingsmore, who grew up in Northern Ireland the son of preacher, is determined to offer treatment to babies who never before would have had a chance of healthy survival. Three babies with rare genetic conditions have received bone marrow transplants based on the diagnoses he's been able to obtain; a fourth is taking an experimental dietary supplement.

"The goal is that every baby will benefit," he said. "Every child that would benefit from a diagnosis would get one and be evaluated for potential treatment."

Studies like Kingsmore's are proliferating across the U.S. Cynthia Morton, a Harvard University geneticist, has proposed sequencing all the genes of babies who fail hearing tests at Brigham and Women's Hospital, to see whether vital treatment can be provided more quickly and appropriately.

"Our dream is that we'll have the genetic results ready when parents follow up with their doctors on the hearing loss," she said. "They'll know whether there's a genetic basis for the hearing loss and can start planning treatment."

Early Intervention

Some babies with genetic deafness are good candidates for cochlear implants, assistive devices that should be surgically installed as early as possible, Morton said. Testing can also help prevent implants from being put in babies who don't need them, she said.

As sequencing technology gets faster and cheaper, interest has grown. Preliminary results from a study led by Robert Green, a Harvard University geneticist at Brigham and Women's Hospital in Boston, suggest that at least four out of five families say they'd be willing to have their babies' genomes sequenced for medical and preventive purposes.

Studying babies' DNA from the time of birth will lead to a better understanding of the role of genes in many medical conditions, said Watson, the genetics college president. Large gene databases will help scientists make more precise observations about which mutations raise the risk of disease, and how much, he said.

Simplifying Interpretation

Simplifying results so that doctors can easily interpret a baby's genome test will be key, said Green, the Brigham researcher, who received a $5 million government grant with Boston Children's Hospital's Alan Beggs to study sequencing in babies. One of the biggest problems is the imposing volume of data from the genome's 6 billion bases. He and Beggs have begun developing a one-page genome report for pediatricians and other primary care doctors.

As currently planned, about 400 of the babies who will be sequenced through his project will have been born completely healthy. Green and his colleagues at Children's Hospital will compare their progress with babies who have not been analyzed genetically, to see if there's any difference in their health in a five-year study. The study must receive final approval from a review board.

Genome Records

The long-term consequences of preserving a record of a child's full genome sequence remains a concern. The presence of certain genes might affect a person's chances for a job, although employers who used a person's genetic profile to block employment would be violating federal law. Or knowledge of a genetic abnormality could create lifelong fears of health dangers, real or imagined, Green said.

Scientists are striving to address those issues. A report released by a working group of the American Society of Medical Genetics and Genomics earlier this year recommended that when doctors find certain mutations, such as the BRCA DNA patterns that raise breast cancer risk, those results should be told to patients, whether or not they were sought by the patient. Green will be studying how and whether to give the results back to babies' parents, when mutations might affect both children and their parents later in life.

"On one side, you've got the utopian visionaries who say everyone's going to be sequenced and helped by it, and dystopians on the other side saying we can't afford any of this until there's evidence of cost benefit," he said. 'We've tried to carve out a set of experiments that challenge both the utopian and dystopian visions.''

Kingsmore has avoided telling parents about anything except the mutations that appear to be involved in the babies' illnesses. The parents are already under the stress of coping with a child's illness and may perceive more bad health news as disastrous, he said. His goal is to remove any obstacles to using the technology.

"What I'm trying to do is make it ubiquitous," he said. "Everyone in the country who needs this ought to get it."

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