Nazar Gozeh scribbled the important words the doctor was saying on the bottom of a cardboard tissue box beside his bed.
It was the middle of the night in Iraq, where Gozeh and his family of five were living at the time, and the phone call from Dr. Scott Demarest at Children’s Hospital Colorado woke Gozeh from a sound sleep.
Still, they talked for an hour. Because what the doctor was explaining would change the rest of their lives.
Gozeh’s two daughters, Lena and Vina, had been wracked with daily seizures from the moment of their births. Nothing would make them stop. Vina’s tiny body curled into an arch, the back of her head nearly touching her toes, just after she was born, and at age 6, she was having 100 seizures per day. Many times, Vina had stopped breathing and her parents feared she was dead. Then she would gasp for another breath.
But now Demarest, a pediatric neurologist who specializes in epilepsy, was telling Gozeh that there was a breakthrough discovery of a gene that does not allow the body to process vitamin B6. A new test on the girls’ genetic samples, taken years earlier, revealed they both had the defective gene.
What they needed to do was start taking an active form of the vitamin, available at health food stores everywhere.
And it worked.
Soon after the middle-of-the-night phone call, after which Gozeh was too happy to go back to sleep, the family returned to Colorado to meet with doctors at Children’s. Within a few months, Gozeh and his wife, Sana Sabir, figured out the right daily doses of active vitamin B6 for the girls. The seizures went from 100 per day to one per day. Then one every couple of months. Then none, except on the rare occasion one of the girls didn’t swallow all of their vitamins or it was time to up the dosage because they had grown.
Gozeh orders the miracle cure, a jar of vitamins, from an online store for $16 a bottle. A six-month supply, when he catches a sale, costs about $2,000.
Lena, 15, takes 11 capsules each day. Vina, 12, takes nine.
“This literally changed our life,” Gozeh said. “We were so desperate.”
Children’s Hospital opens Precision Medicine Institute
The genetic disease that caused Lena and Vina’s seizures is so rare that doctors for years had no idea how to help. The answer came after Dr. Demarest asked a lab in London to check for an extremely specific problem in their DNA.
The girls’ case is the classic example of precision medicine, which is the combination of personal genetic data, technology and vast amounts of research from labs across the world to determine a single patient’s course of treatment.
In July, Children’s Hospital in Aurora launched its new Precision Medicine Institute, a place for specialists throughout the hospital to get help solving rare diseases. Hundreds of doctors, including oncologists and neurologists, are already using precision medicine, but hospital officials said the institute will increase access to genetic testing for more kids and lead to individually tailored treatments. It also should lead to more fundraising, evidenced by a recent $5 million gift from the hospital foundation’s board chairperson to help open the new institute.
Oncologists are creating treatment cocktails for children whose cancer is caused by cells that mutate and “go off the rails,” sometimes because of more than one mutation, Demarest said. Specialists are using personalized drugs and gene therapies for neurodegenerative diseases and cystic fibrosis caused by genes present since before birth.
In one widely publicized case, doctors at Children’s in Colorado and Boston Children’s created a drug that worked for only one person, a Boulder girl named Mila Makovec. The drug, which they named milasen, was like a Band-Aid that covered up a gene sequence that was broken and causing a neurological disease that was destroying Mila’s brain. The drug initially helped Mila — she started eating food instead of using a gastronomy tube and she began holding up her head again. But it came too late to save her; Mila died in 2021 at age 10, about a year and half after receiving the treatment.
“Precision medicine is kind of a buzz term,” said Demarest, who was also one of Mila’s doctors. “How do you bring the right treatment to the right patient at the right time?”
It’s not only about genetics, but other huge data sets that might be relevant to a patient’s care. Besides the “explosion” in genomic knowledge in the past two decades, there have been major advances in understanding how environmental exposures influence health, he said.
“Frankly, it’s so much data that no one physician can keep it all in their mind. And that’s where we need tools that help us to integrate that into our systems and processes so that the right knowledge is at our fingertips when we need it to make the right decisions.”
That’s exactly how it worked for the Gozeh girls.
From birth, doctors suspected their seizures were related to a vitamin B6 deficiency, but it took advances in genetic research to solve the mystery.
When each girl was born, almost four years apart in Colorado Springs, they immediately went into nonstop seizures. Physicians rushed in with every drug they could think of to stop them. None worked. Then neurologists tried giving them vitamin B6.
The seizures stopped, but only temporarily.
Years before the lab in London identified the girls’ genetic issue, Demarest had their genes tested to look for a well-known genetic issue discovered two decades ago that was linked to a vitamin B6 deficiency. But the tests came back negative.
What was coded in the girls’ DNA was more complex than that.
The test in London in 2017 found that the girls’ genetic coding did not allow them to turn regular B6 into a slightly different form that supports the function of cells, including brain cells. They were missing a binding protein for pyridoxal 5 phosphate, the active form of B6.
A research paper that year had identified the gene with that binding protein, and shortly after, Demarest had the lab in London run genetic tests on the girls’ genetic samples to look for it. Instead of needing regular B6, as they had been taking for years, they needed the active form of the vitamin.
“We just give them the final product,” Demarest said. “We skip that in-between step.
“A simple, over-the-counter vitamin was able to make a huge difference for this family. This wasn’t a fancy new high-cost drug.”
But Demarest is careful to point out that what happened with the Gozeh girls was exceptional.
“I certainly don’t want to communicate a message that most patients with a rare disease could just take a vitamin,” he said. “This is a rare scenario where this was possible, but that’s also the nature of rare disease.”
There are about 10,000 rare diseases, and thousands of those diseases have fewer than 100 people in the world who are affected by them. But as much as 10% of the population has a rare disease.
The future of medicine is in figuring out how to set up a system in which patients who would most benefit from genetic testing and tailored treatments would have access to that kind of precision care.
Right now, though, the technology of this is in some ways ahead of the science. This means labs can run genetic tests that map a person’s entire DNA, but doctors can’t say what it all means. “We have to do this really carefully and responsibly,” Demarest said. “I need to know that when I tell you that this is what’s causing a disease, we know that that’s not wrong.”
Children’s is working on building its capacity for in-house genetic testing, recently adding testing for neurological and developmental disorders. The hospital’s laboratory can also do what’s called whole exome sequencing, which searches for a variety of conditions by looking at the coding DNA, which is like the list of ingredients for a recipe and is only about 3% of a human’s DNA.
Children’s soon will start doing whole genome sequencing, which is the entire DNA, the other 97%. In the recipe analogy, this is the part that would explain how to put the recipe together, and most of this is still not understood by researchers.
The hospital is doing more than 1,000 genetic tests on patients per year in its in-house lab, but has about 4,000 patients whose tests are run at other labs.
Girls can focus on developmental skills, thanks to the vitamin
The seizures were so frequent and debilitating that they affected Lena and Vina’s development, including their speech, muscle tone and cognitive ability. Taking care of them was a nonstop job, for years, so all-consuming that Gozeh quit his job working for the U.S. State Department and the family was pushed to the brink of bankruptcy.
Gozeh, who is Kurdish and worked in counterrorism for the United States in Iraq, had set up video cameras in his home in Colorado Springs so he could watch the girls from across the world while his wife slept.
The breaking point came one night when Sabir called her husband in Iraq because Lena was seizing and would not stop. She called 911 and emergency responders arrived to help. About an hour after Lena was OK and resting, Vina started seizing.
“I said, ‘That’s it. I can’t do this,’” Gozeh recalled. “For Vina, it went up to almost 100 seizures per day. My credit cards were maxed out. No saving at all, no money coming in. These were really tough times.”
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Gozeh later took a job with an oil and gas company and the family moved to Iraq. They kept in touch with Dr. Demarest, but in emergencies had to rely on local doctors who were not as familiar with their daughters’ history. Gozeh recalled taking Vina to a hospital emergency department in Iraq, where a doctor “administered every single medication at his disposal” and still the little girl’s seizures didn’t stop.
“The doctor looked at me and said, ‘There is nothing else I can do,’” Gozeh said. “It was the lowest I have been in my life. I survived IEDs (improvised explosive devices). My friend right next to me got hit and died. I have had guns pointed at my head multiple times. Nothing, nothing compared to a situation where you are begging a doctor, and the doctor says there is nothing I can do.”
The middle-of-the-night call from Dr. Demarest arrived like a lifeline.
Vina’s progress has been more dramatic, likely because she was only 6 when she began taking the right vitamin.
She now reads short stories on her own and is working with a therapist to increase her vocabulary. The 12-year–old loves electronic gadgets. She’s “obsessed with colors,” and was enthralled recently by the bright assortment of limeades and fruit drinks on the menu at Sonic.
Her older sister, Lena, who will turn 16 this month, is enamored with school, though she does not understand why she can’t go throughout the summer. Gozeh and his wife sometimes drive her there anyway, so she can walk up to the door with her lunch box and see for herself that it is locked.
Their son, Aza, who was born in between the girls and does not have the genetic issue, wants to become a dentist. As a family, they started a balloon garland company, a simple kit for a do-it-yourself party decoration that Sabir designed and the girls help package. Part of the proceeds go to precision medicine efforts at Children’s Hospital.
“We are blessed,” Gozeh said. “We are super, super lucky to live in Colorado.”
