Her son, Christian, was born in 2010 with multiple, mysterious
syndromes that leave him unable to speak, chew, or walk on his own.
Initial genetic tests failed to provide a diagnosis. Aimee's hopes
are now pinned on a new test called exome sequencing that searches
all the protein-making genes for glitches that could explain
Once strictly the domain of research labs, gene-sequencing tests
increasingly are being used to help understand the genetic causes of
rare disease, putting insurance companies in the position of
deciding whether to pay the $5,000 to $17,000 for the tests.
As use of the new technology has grown, a number of insurers,
including Blue Cross Blue Shield, have reacted by putting the brakes
on reimbursement, according to interviews with researchers,
diagnostic experts and insurance executives. Insurers are demanding
proof that the results will lead to meaningful treatments among the
estimated 2 million Americans with a serious, undiagnosed disease,
still an unlikely prospect in the majority of cases.
Genetics experts say that sequencing more than doubles the chances
that families get a diagnosis, and saves spending on multiple tests
of single genes. Even if no treatment is found, the tests can also
end hugely expensive medical odysseys as parents frantically search
for the cause of their childís furtive illness.
Until the reimbursement issue is resolved, some smaller diagnostics
players will likely stay on the sidelines, leaving the field to
early adopters of the technology such as Ambry Genetics and
Bio-Reference Laboratories' GeneDx. And families short on resources
like the Robesons will be left scrambling for funding.
UNRAVELING RARE DISEASE
Howard Jacob was the first to use gene-sequencing tools to unravel
the mystery of a rare disease in 2009, leading to a bone marrow
transplant that saved a little boy named Nic Volker.
Five years later, Jacob's molecular genetics lab at the Medical
College of Wisconsin has done more than three dozen whole genome
sequences, a test that reads the more than 3 billion letters that
make up the human genetic code. They have sequenced 400 whole exomes,
tests that look only at the protein-making segments of DNA known as
exons, which represent 2 percent of the genome but account for 85
percent of disease-causing mutations.
Baylor College of Medicine in Houston, Texas, has handled 3,500
exome-sequencing cases since it started offering the test in 2011. A
study of its first 250 cases showed whole exome sequencing
identified the disease-causing gene in 25 percent of cases. Since
the findings were published last October, the rate has increased to
28 percent as the list of known mutations has grown, said Dr.
Christine Eng, who directs Baylor's Whole Genome Sequencing
Eng said insurance companies initially paid for most of the tests,
but as volume has increased, more claims are getting denied. "There
are some companies that are saying out and out, we won't cover this
Dr. Allen Bale, director of the DNA Diagnostic Lab at Yale School of
Medicine in Connecticut, has seen a 500 percent increase in orders
for exome sequencing since 2011. The lab does about 750 whole exome
tests a year, and there, too, reimbursement is becoming an issue.
Bale said Medicare does not cover the tests. Other insurers pay
enough so the lab can break even.
"There's a lot of testing we're doing that's getting denied. We
appeal it," he said. "A lot of time that works, but it's case by
LACK OF EVIDENCE
Although gene sequencing is still far from mainstream, its rapidly
dropping cost - which has fallen from $3 billion for the first gene
map in 2003 to as little as $1,000 this year - has made the tests
increasingly attractive. In cases like Christianís, doctors say it
offers a more comprehensive way to diagnose unexplained syndromes,
replacing the guessing game in which tests are ordered based on what
they think the problem might be.
Insurers are not yet convinced.
Dr. Julie Kessel, who directs coverage policy for Cigna, said
sequencing requests were scarcely noticed five years ago. Now,
"they're very, very much on the radar." Cigna generally does not
cover whole genome or whole exome sequencing unless there is a clear
Last August, one of the industryís biggest players, Blue Cross Blue
Shield, issued a report saying exome sequencing might pinpoint the
genetic cause of disease in up to half of patients, but only a
fraction of those will be able to use that as guidance because
treatments don't exist yet. Since then, Blues plans in Louisiana,
North Carolina and Pennsylvania have deemed exome sequencing
"investigational," meaning not eligible for coverage.
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Christian's own insurance company, Pennsylvania Medicaid provider
UPMC for You, "didn't budge at all," Aimee Robeson said. The family
hired an attorney and appealed, but lost. The company wanted proof
the test would offer a benefit. Christianís geneticist wrote a
letter listing reasons it might, but the judge wasn't swayed.
Insurers say their objections stem from a lack of evidence that the
tests can improve patient care.
There are some celebrated examples that it can, such as the Volker
case or Noah and Alexis Beery of California, whose genetic defect
left them with health problems similar to cerebral palsy. Genome
sequencing led to highly effective treatments to replace the missing
neurotransmitters that were causing their symptoms.
In most cases, however, finding a treatment "is vanishingly rare
because we're only just making these discoveries," said Dr. Teri
Manolio of the National Human Genome Research Institute, a part of
the National Institutes of Health.
At Aetna Inc, Dr. James Cross, vice president of national medical
policy and operations, said sequencing has gotten ahead of the
Traditionally the company has made coverage decisions based on the
individual test and whether it affects patient outcomes, he said.
"With sequencing, you've got a lot of information that we don't have
that kind of evidence around."
For Ambry Genetics, the first commercial lab to offer whole exome
sequencing, insurance coverage is "all over the map" for the
company's $5,800 test, said billing director Marsha McDonagh. She
works with Blue Cross, Cigna, Aetna, UnitedHealthcare and several
Medicaid plans, among others. "The ones least receptive right now
are the Blues," she said.
Consultant Stephane Budel of DeciBio believes the reimbursement
issue is stifling competition among diagnostics providers. Industry
players range from those just ramping up, such as MolecularHealth
and Selah Genomics, to midsize companies such as Ambry and GeneDx
and giants such as Illumina and Thermo Fisher Scientific's Life
"There's definitely a number of smaller players that are waiting for
this to be sorted out," said Budel. He believes insurers' concerns
will fall away as sequencing costs continue to fall in the next few
years. "There is very little doubt it is going to become standard of
Even without treatments, a diagnosis gives parents the ability to
make better-informed family-planning decisions and puts a stop to
repeated testing that can cost tens of thousands of dollars.
"There's a monumental relief with diagnosis. It changes everything,"
said Dr. Richard Gibbs, director of the Baylor Human Genome
Sequencing Center, who sequenced the Beery twins.
Andrea Smith of Winthrop Harbor, Illinois, realized her son Ethan
had a serious problem when a virus turned his urine "the color of
Coca-Cola." With her next boy, Chase, a virus caused kidney failure;
the same happened with her youngest child, Norah. A fourth had no
Doctors suspected a genetic form of atypical hymolytic-uremic
syndrome, a kidney disorder. Their case was so compelling that
doctors at Children's Hospital of Wisconsin offered to sequence
Norah's genome, funded by a research grant.
They learned that three of her children inherited the disorder, and
the fourth is a carrier. But testing also showed the defect could be
corrected with a kidney transplant. Smith says it's too early to
consider that option for her children, but she's glad to know she
Aimee Robeson may soon get an answer as well. Members of her church
are paying the $7,000 for Christian's test.
"I'm relieved it's getting done," Aimee said. "I want to make sure
if there is anything that I could do for my son, that I did it."
(Reporting by Julie Steenhuysen; Editing by Michele Gershberg and
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