Photography by David Torrence
Go to Shriners Hospital on a hypophosphatasia follow-up day, and hang out in the hallway. It’s how Lourdes is supposed to look. Children who could only sit are walking. A little girl who couldn’t walk skips everywhere. An older girl who couldn’t shop more than 20 minutes now goes to the end of the credit card. A boy whose legs would barely support him runs everywhere—so fast, he developed shin splints. And when they tried to slow him down with a boot, he froghopped through the hospital.
The hospital’s medical-scientific director, Dr. Michael Whyte, is one of the world’s few experts on this disorder. Working with a small pharmaceutical company in Canada and colleagues around the world, he’s identified the first promising treatment for a genetic disorder that can cause babies to be stillborn, or to have skeletons so soft they don’t show up on an X-ray.
“Their arms fold up like accordions,” Whyte says, “and their skulls are like brown paper bags.” In other instances, the disease doesn’t show up until childhood or even adulthood; it can be as mild as a tooth falling out, or severe enough to kill.
Zachary Beck’s parents started worrying when he hadn’t start walking by 18 months—but they went three long years without a diagnosis, then started getting stabs in the dark, like “He has muscular dystrophy.” Nothing made sense.
“He was skin and bones, with weak muscles,” says his mother, Niki Beck. She’s a nurse; Zachary’s father is a physician. And they were confounded.
The Becks took Zachary all over the country. Finally a physician remembered doing a rotation with Michael Whyte, and the puzzle started to come together. Zach had hypophosphatasia.
But there was no treatment.
Zachary started coming to Shriners Hospital every year to participate in research studies. The Becks live in rural Wyoming, but he couldn’t do much outside. He wanted to be on the swim team with his friends, but he was too weak to climb up onto the block, so he had to dive from the side, and he was too weak to kick hard, so he’d barely made it to the other side when the rest of the team had finished the full lap. At school, he had an elevator pass, and he got dismissed early so kids wouldn’t jostle him in the halls.
Three years ago, just after Zachary turned 12, Whyte told the Becks about a new study—the first truly promising treatment ever.
Whyte had gotten a call from a Dr. Philippe Crine, who was working with a small company called Enobia (bone spelled backward, plus “ia”) Pharma. “We think we can target alkaline phosphatase to bone,” Crine said, explaining that certain amino acids would help it stick.
They’d already done successful drug trials with adults and infants, and now Whyte was starting one with children.
“We were just blessed to be in the right place,” says Niki. “This is the first treatment they’ve ever had for it, and it just happened to come right before his growth spurt.” He’ll now grow to his full height—the Becks aren’t sure just how tall that will be, because he’s adopted, but Niki says “it’s just fun waiting to see.”
After six months of the new treatment, she went out in the backyard and heard, “Mom! I’m up here!” Zachary was perched about 25 feet up a huge Wyoming fir tree. This summer, with about two and a half years of treatment behind him, he climbed “this incredible narrow sawtooth hiking trail—against doctor’s advice,” Whyte adds dryly, “up to Angels Landing, 1,400 feet above the canyon floor—and only on the way back do they see the sign that says six people have died since 2004 falling from the cliffs on that trail!”
He got his lifesaver badge for Boy Scouts by diving to the bottom of a lake and bringing up two weights. He built a canoe over the winter, and he and his dad canoed for miles, with portages. Niki got certified to do belay so he could do rock climbing.
He’s thinking of aerospace engineering as a career.
Whyte is also professor of medicine, pediatrics, and genetics at Washington University School of Medicine, and last March, he published his amazing results in The New England Journal of Medicine.
He says his interest in hypophosphatasia was “an accident, like most things in my life.” He saw a woman with the adult form who’d been misdiagnosed as having osteoporosis. “All her panels showed low phosphatase,” he says. “So you don’t Google. You go downstairs and blow the dust off the books. I studied her and her family, then started hearing about other cases.” Thirty-five years later, he still finds
hypophosphatasia remarkable in its range of expression: The mildest cases might show up as a tooth falling out before age 5; the most severe cause a baby to be stillborn or die in infancy, or make it impossible for children to walk or breathe on their own.
A Canadian physician, John Campbell Rathbun, named the disorder in 1948, when he treated a baby boy with paradoxically low levels of alkaline phosphatase. The boy was first treated on December 19, 1946—Michael Whyte’s birthday. And 50 years after his death, his mother called Whyte to ask if researchers had made any progress. “She was on her way from Nova Scotia to Branson,” he says. “So we were able to get her DNA, and then her estranged husband’s, too.” New technology made it possible to identify which gene was flawed and identify about 270 possible mutations that could cause the disorder.
Years ago, Whyte tried plasma and placenta transplants, but it soon became obvious that no matter how high you took phosphatase levels in the bloodstream, it didn’t reach the bone. A molecule (inorganic pyrophosphate) was inhibiting mineralization. So Whyte tried bone marrow transplants and had far greater success. Then he heard from Enobia.
They started drug trials with adults, then moved to infants who were likely to die from the disorder. Enobia flew a little girl from Belfast, Northern Ireland, to Winnipeg. She’d been breathing so rapidly, she seemed in need of intubation—and then the drug took effect. Her breathing stabilized, her bone started to strengthen, and two years after treatment began, there’s video of her kicking a soccer ball with gusto. A 3-year-old from the United Arab Emirates needed oxygen and couldn’t stand; after treatment, the video shows her scrambling up a kiddie slide.
The next group to receive treatment included nine children and three teenagers. Some had survived the infantile form of the disorder; others had the childhood form, but with weak muscles, wobbly walks, and rickets showing on X-rays.
“The findings are wonderful,” Whyte says. “After only six months, half were already walking normally.”
