Front page of the Houston Chronicle
Twins' recovery a key step in genetic medicine, thanks to Baylor Med
By ERIC BERGER
Copyright 2011 Houston Chronicle
June 15, 2011, 10:33PM
K.C. Alfred For the Chronicle
Retta Beery, left, can finally relax with her twins, Alexis and Noah, at their Encinitas, Calif., home. The twins had been sickly for years before genome sequencing determined what was really wrong.
For every day of his first six years of life, Noah Beery drooled and threw up large amounts of what he ate. And he was the healthy twin.
His sister, Alexis, would wake multiple times at night and endure tremors for hours at a time. By midmorning she could no longer exert herself even to sit up. An initial diagnosis of cerebral palsy at age 2 proved false when the twins' condition continued to deteriorate.
When the children were 6, doctors diagnosed them with a relatively rare genetic disorder. Treatment helped but did not cure them. When Alexis was 12 she stopped breathing and almost died. Paramedics had to revive her twice.
Until the dawn of the era of personalized medicine, this is where the story would have ended, in likely tragedy.
But with genetic sequencing becoming more commonplace every year, the Beerys sought a deeper genetic analysis of their childrens' problems, and at Baylor College of Medicine the San Diego family had their complete genomes sequenced.
This finally identified the problem: a genetic twist on a rare disease. With a slight alteration to their medical treatment, the twins — now 14 — are as active as any others their age.
"I totally feel grateful for every day," said Retta Beery, the twins' mom. "Every time we look at Noah and Alexis doing anything, just having conversations with friends, to running track and winning races, I feel so incredibly blessed and amazed and in awe of every moment."
A promise finally realized
On one hand the Beerys' transformed lives represent an isolated victory, a very personal tale. But this is a story that resonates far beyond one family. Their experience may be the first time doctors have used whole genome sequencing to diagnose an ailment and improve medical care.
And the success experienced by the Beery family likely signals that the promise of personalized medicine, powered by physicians being able to read the genetic codebook of human disease, eventually will be realized.
"If you ask me, this is practicing personal genomics," said Dr. Jim Lupski, the Baylor physician who helped analyze the Beery genomes.
"I don't want it to come out as hype, because we don't need hype," Lupski said. "We have a lot of work to do, and a lot to understand about genetics and medicine. We have a few decades yet of filling in the Rosetta Stone.
"But I think this shows there will come a day when the genome sequence will be as integral to the workup of a patient as the family history is right now."
Noah and Alexis were born colicky. They cried and screamed night and day and threw up daily. By their 9-month checkup they were far behind the normal development milestones.
After tests upon tests, from MRIs to endoscopies, Noah's uncontrollable vomiting and Alexis' apparent seizures only worsened.
Retta Beery continued to research their condition, and the daily timing of Alexis' symptoms gave her the clue that eventually led the family to neurologist Dr. John Fink at the University of Michigan.
When the twins were nearly 6 the family traveled to Michigan, where Fink diagnosed the children with the genetic disease dopamine-responsive dystonia. This can be treated with a synthetic form of dopamine, a neuro transmitting chemical.
"When we got to Michigan we literally had to carry Alexis around," Retta Beery recalled. "Then we gave her one quarter of a pill that first night. She slept for the first time in her life for the full night through. She walked to the rental car on her own. She got into the car on her own for the first time in her life and buckled herself in. We had no idea what cognitive ability she had because it was trapped inside this body that would not function."
Alexis and Noah made remarkable recoveries, beginning to live the normal lives their parents had dreamed of, playing sports and excelling in school.
"It was everything we never imagined could happen," Beery recalled.
3 billion bits of data
Then, about two years ago, Alexis had a cough that began to worsen and turned into a breathing problem. Various physicians were stumped. All of a sudden the family was back in a nightmare of not knowing whether a child would survive.
Retta's husband, Joe, worked for a biotechnology company and suggested they look into genetic sequencing. She eventually linked up with Baylor, which has one of the world's largest genetic sequencing labs, and Texas Children's Hospital.
Baylor's Matthew Bainbridge led the effort to sequence the family genomes. After reading out every one of the 3 billion bits of data in each DNA sequence, the researchers found that the twins had neither of the two gene mutations known to cause dopamine-responsive dystonia.
But scientists found three related genetic abnormalities that might cause the disease, and one of these mutations led them to conclude that Alexis and Noah were deficient in serotonin, another neurotransmitter, in addition to dopamine.
With the addition of a supplement, Alexis' breathing problems were solved. She's running track again, and Noah's focus in school has improved significantly. The research describing the transformation is published in Wednesday's Science Translational Medicine.
Eight years of work
It's been eight years since the completion of the Human Genome Project, but only one year since the first time geneticists sequenced a person's entire genome to identify the genetic cause of a disease. This occurred when Baylor identified the gene mutation that caused an illness that afflicted Lupski, the Baylor physician.
The new work takes that a step forward by using a whole genome sequence to improve medical therapy.
"It feels really good to see this moving ahead," said Richard Gibbs, who directs the Baylor Genome Sequencing Center and was a key figure in the Human Genome Project.
A glimpse into future
It's been a struggle to take the human genome's raw data and change medical care. Since the first genome's completion, scientists have discovered that the role of genetics in human health is more complicated than they had anticipated.
Cures didn't come immediately after the genome's completion, and the use of genetics to improve care of common diseases, such as heart ailments and cancer, has yet to become commonplace.
Yet Gibbs said geneticists are beginning to grasp the whole picture of genetics and disease, and the Beery family's success provides a glimpse of the future of medicine.
"This," he said, "Is just one more brick in the wall."
posted on June 17, 2011