May 27, 2020

When healing hurts Seal Harbor sixth-grader lives with rare disorder

For Patti Pinkham of Seal Harbor, the body’s miraculous ability to heal itself is bittersweet. Pinkham and her husband, Larry Albee, have two daughters. Nine-year-old Sarah hobbles around their cozy wooden home with a walking cast and crutches, cheerfully nursing the final stages of a broken leg.

Emma, days away from her 12th birthday, jets around the house in a wheeled executive’s chair. One by one, her soft tissues are becoming rigid, literally turning to bone. Emma’s shoulders are rounded forward, and her arms are fixed across her torso. When she stands, her back is bent at a steep angle, making her balance precarious.

Ironically, the same proteins that have made her sister’s broken leg whole again are stealing Emma’s mobility.

Emma Albee is one of only two Mainers living with a rare genetic condition called fibrodysplasia ossificans progressiva. Scientists believe FOP is caused by the random mutation of a single gene that tells the body when and where to grow new bone.

Statistically, about 2,500 people worldwide – one in every 2 million babies born – should have the faulty gene. But researchers have documented only about 200 cases. And 150 of those live in the United States, said Sharon Kantanie of the International FOP Association.

Throughout their lifetimes, these people’s muscles and tendons

will transform sporadically into bone that is biologically identical to the average person’s femur or spine. It has marrow. It will fracture, break and mend.

It’s simply in the wrong place.

“This is a catastrophic condition,” said Dr. Frederick Kaplan, an orthopedist at the University of Pennsylvania Medical Center. Kaplan has treated more than 300 people with FOP. “It’s like an atom bomb inside these kids.”

In 1692, a French doctor named Guy Patin described the first known FOP case, writing to a colleague, “I saw a woman today who had finally become as hard as wood all over.”

More than 300 years later, much about the disorder remains unknown.

Kaplan and a colleague at Penn, Dr. Michael Zasloff, have studied the disorder since the 1970s, when both men were introduced to people living with FOP.

The vast majority of FOP cases are diagnosed in infancy because the same chromosomal quirk that sparks bone growth typically disfigures a person’s big toes. A missing joint causes the toes to curve inward and appear oddly short and arthritic even at birth, Kaplan said.

Zasloff, who has met about 150 FOP patients in the 25 years he’s been studying the disorder, has seen only two with normal toes.

But Emma has ideal 12-year-old toes: straight, jointed and decorated with glittery nail polish.

For the first nine years of her life, Emma had no idea her own body could make her immobile.

She played softball, took gymnastics classes, and spent her summers exploring the woods and marsh behind her home on Dodge Point in Hancock County.

“We had no inkling,” Pinkham said. “Everything had been normal. She had done everything.”

Nearly three years ago, Emma took a perfectly normal spill on the playground. She banged her neck and shoulders on a metal bar and developed a perfectly normal goose egg on her neck.

But the bump didn’t recede. Instead, tenderness and swelling spread across the little girl’s neck and shoulders, and the lump on her neck grew so large that a family doctor feared it was a tumor.

“We were baffled,” Pinkham said. “We just wished there was an answer out there.”

An orthopedist at Eastern Maine Medical Center in Bangor ordered an immediate CAT scan and biopsy. But instead of the cancer cells doctors expected to see, the mysterious lump showed only inflamed tissue and a proliferation of blood vessels – a pipeline of nutrients to feed growing bone.

Within a week, doctors had diagnosed FOP. All Pinkham heard was that Emma would live to become an adult.

“I’ve always just been so relieved that it wasn’t any of the scary, life-threatening cancers that had been talked about at the beginning,” Pinkham said.

But for a full year, Pinkham and Albee learned the tragedy of FOP as they watched their oldest child suffer the constant pain that accompanies growing bone.

“It was really hard to see all this happening and know there was nothing we could do, no medicine to take,” Pinkham said. “Sometimes it’s pretty desperate, knowing this is going on.”

The biopsy performed by well-meaning doctors likely exacerbated the flare-up, and for endless months stiffness and swelling would jump sporadically to different parts of Emma’s body, claiming her back, neck and shoulders in turn.

“It would always take us by surprise,” Pinkham said. “It was always such a shock to see part of her body lock in place.”

Zasloff said he met a young woman with the disorder while employed as a geneticist for the National Institutes of Health. “I had never seen anything like it,” he said. “I was struck by how terrible a condition it was, and how little we knew about it.”

Both Zasloff and Kaplan spent the next two decades interviewing the world’s known FOP population and observing how the disorder directs the body to grow lesions of excess fibrous tissue, which turn to cartilage and then, within a few days, to bone.

“It looks like a second skeleton,” Kaplan said. “You see the normal skeleton, and wrapped around it and through it are ribbons and sheets of bone.”

The unnatural bone growth follows the same pattern as skeletal development in the womb. The neck and shoulders typically are the first to freeze; then bone radiates outward, creeping through the rib cage and locking limbs, then digits, into permanent, sometimes awkward positions.

“It grows almost like a cancer,” Zasloff said. “Joints are set into positions that aren’t logical, that aren’t predictable.”

When the excess bone is removed surgically, it just grows back more aggressively.

“We’re quite stymied,” Kaplan said. “Everything we try to do makes it worse.”

Medical research has linked the painful periods of bone growth – the flare-ups – to injury. When someone with FOP bumps a knee or even receives an injection into muscle, a flare-up will result. Even flare-ups that seem random likely are caused by some minor injury, Zasloff said.

A forest of mysteries

Emma hasn’t experienced a flare-up in a full year, but her reprieve is temporary, doctors say.

“You can’t predict where the next flare-up will be, or how long it will last,” Kaplan said. “It would be like if you had sensitive equipment to detect minor changes in Earth’s crust hours before an earthquake.”

The spread of new bone is unpredictable in childhood, yet almost everyone with FOP reaches the same point by adulthood, Zasloff said. FOP isn’t considered fatal, but without constant care fused bones in the rib cage, throat and jaw can lead to malnutrition or even suffocation in advanced FOP cases.

“There are few people who are spared by age 20,” Zasloff said. “Almost all of the joints are fixed. They’re almost fully immobile.”

Despite recent advances in human genetics, the FOP code has not been cracked. Scientists haven’t been able to identify the FOP gene because although the disorder is inherited, very few FOP patients have children.

“If we had even 15 families, this would be a project that a college student could do in a couple weeks. It would enable us to understand the master switch that starts this cascade,” Kaplan said. “But we have to use more clever and imaginative ways to navigate this forest of mysteries.”

For example, a Boston researcher named John Wozney recently used his research with the fruit fly to detect an important human protein that ties the illicit bone growth of FOP to the body’s own defense mechanism.

White blood cells are the body’s police force. They patrol the circulatory system on a constant search-and-destroy mission to kill bacteria, viruses and other intruders. But for a person with FOP, a specific type of white blood cell called a lymphocyte is the enemy.

The lymphocytes of a person with the gene coding for FOP contain tremendously high amounts of a protein in charge of bone building called BMP-4.

When a person without FOP is injured, normal lymphocytes stream to the site and hasten the healing process, preventing infection and building scar tissue. But when a person with FOP is injured, lymphocytes containing excessive amounts of BMP-4 flood the site and begin eating away healthy tissue and replacing it with bone.

But understanding the physiology of FOP makes little difference to parents who receive the sudden and devastating news that their beautiful babies inevitably will be trapped within their own skeletons by the time they’re old enough to vote.

The kids prevail

Emma and her parents met severely disabled adults with FOP for the first time at an October international symposium in Philadelphia. For Pinkham, their physical limitations were a tragic omen of the future.

“I had hesitated to know too much about the people who are so affected,” Pinkham said. “But once you see beyond the FOP, they’re just normal people – the same sense of humor, the jobs they talk about … I know they’re there as friends when I need them.”

The Pinkham-Albee family e-mails several parents of FOP children regularly, and Emma writes to friends on the West Coast who share her challenges.

“This is what it is. We’ve always been open about what could be ahead,” Pinkham said. “But we try not to think about what may happen down the road.”

Emma, on the other hand, has taken FOP in stride.

She left Tremont Elementary School one year as a normal, busy 10-year-old girl who loved art and wanted to be everywhere and do everything. She returned the next year as a normal, busy 11-year-old girl who happened to use an electric wheelchair to make it to all her activities.

“She’s taken it on. It hasn’t slowed her down,” said Becky Hopkins, a family friend who has known Emma since birth and serves as her aide at school.

Emma sings in her school chorus and looks forward to attending the Summer Festival of the Arts each year. She plays with Bugsy the rabbit, and struggles with her math homework. She giggles with her lifelong friends during study hall and is planning a party for her birthday.

Despite limited movement in her arms, she recently taught herself to knit and crochet.

“She does what everybody else does,” Hopkins said. “She’s found ways to adapt. She’s very insightful that way.”

Eschewing her heavy wheelchair, Emma zips around the classroom in her favored chariot – an adjustable blue desk chair. Playing dodge ball in gym class could have serious medical complications, so Emma runs the time clock and keeps score for her school’s basketball team.

In art class, she recently tackled an ambitious pottery project. Rolling clay on a tabletop was nearly impossible, so she spent recesses developing her own method and painstakingly assembling her coil pot.

“Obviously it affects everything she does, but it certainly hasn’t affected her attitude or her ability to be creative,” said Sandy Erwin, Emma’s art teacher. “She’s right there. She just takes it all in like a sponge.”

Acceptance grew more slowly for Emma’s parents as a thousand practical matters weighed on the family every day, reminding them of Emma’s condition.

“It took a while to get over that hump – to accept that this was happening, to be able to put FOP aside as one thing that was happening in Emma’s life,” Pinkham said. “It’s amazing how something so simple can be so complicated,” she said.

Pinkham left her job to dedicate more time to Emma’s needs. Their two-story home on rural Dodge Point has been redesigned for wheelchair use, and family members have built hard-packed trails through their wild back yard so Emma can continue to enjoy the woods she loves.

And Pinkham and Albee have become activists, teaching an entire community about FOP and serving as advocates for Emma’s needs. In about six months, Emma’s friends and family raised $20,000 for FOP research.

Pinkham says she’s just following her daughter’s lead.

Kaplan agrees, calling Emma and the dozens of other children with FOP inspirational. “I tell parents, ‘They’ll do far better than you will.'”

“The kids adapt. They’re resilient,” he said. “With FOP, the parents endure – but the kids prevail.”

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