Health

A tenacious student uncovered the root of an onslaught of broken bones

When doctors failed to look further, a 24-year-old dug into his medical records and hit pay dirt.


For as far back as he can remember, Aaron Blocker’s bones had given him trouble.

Born with severely bowed legs, Blocker as a baby wore metal leg braces while he slept, which enabled him to walk. Even so, he said, his legs “always hurt.” The rash of broken bones started when he was 10 years old and fell on his hand, fracturing several fingers. A few years later he broke his nose for the first time when it was clipped, not forcefully, by a swing made of soft plastic.

“My family just thought I was a clumsy child,” said Blocker, 30, who grew up near Jackson, Miss., where he still lives. “I was very active.”

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Over the years, Blocker said, doctors set his broken bones and treated other orthopedic problems, including scoliosis, a sideways curvature of the spine. But none suggested taking a closer look, even after Blocker underwent multiple surgeries to replace both hips in his 20s — an operation typically performed on people decades older.

The premature and unexpected failure of those hip replacements convinced Blocker his skeletal problems had a cause that was being overlooked. At 24, while a graduate student in biomedical research, Blocker harnessed his skills and trained them on himself. He spent several weeks digging into his medical records and scrolling through scientific websites before hitting pay dirt: a possible diagnosis that was subsequently confirmed by genetic testing.

“It was a relief to have an answer,” said Blocker, who works for an insurance broker. “But I’ve always wondered, how did this go missed for so long?”

The answer, one of his doctors later theorized, may reflect evolving scientific knowledge about his rare diagnosis, as well as Blocker’s own complicated medical history.

Tooth trouble

Blocker’s bones weren’t his only problem.

“I had a lot of issues with my teeth growing up,” he said. His molars, typically the largest and strongest teeth, would crack inexplicably. By the time he graduated from high school, seven teeth had been extracted. Blocker also had numerous cavities, which his dentist attributed to “weak teeth.” In high school he had two wisdom teeth removed and healing was unusually slow; the oral surgeon noted a weakness in his jawbone but did not recommend further investigation.

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In his mid-teens, Blocker developed recurring problems with his right shoulder. The first time, he dislocated it while throwing a ball. Another dislocation occurred while he was sleeping, although no one could explain how or why this had happened.

During his senior year of high school, Blocker was forced to contend with a more urgent problem. After a two-week hospitalization that capped months of abdominal pain during which his weight plummeted to 100 pounds, Blocker, who is 5-foot-10, was diagnosed with Crohn’s disease. The chronic inflammatory bowel disease causes severe diarrhea and weight loss.

He was prescribed prednisone, a mainstay drug used to treat Crohn’s. Blocker said he took a relatively low dose of the corticosteroid, which reduces inflammation, for about eight weeks.

A year later in January 2011 when the disease flared, Blocker was hospitalized again and underwent an abdominal CT scan. The scan revealed an alarming and unexpected incidental finding: avascular necrosis of both hips. A bone density scan also found that Blocker had severe osteoporosis.

Avascular necrosis occurs when the blood supply to a bone is cut off, causing the tissue to collapse and die and threatening the integrity of the structure. Causes include long-term steroid use particularly at high doses, excessive alcohol consumption, fractures, and a variety of medical conditions. People with inflammatory bowel disease may have a reduced ability to absorb calcium and vitamin D, which can affect bone density and lead to osteoporosis, a condition in which bones become weak and brittle.

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“The orthopedist told me my hip bones were dying and said it could be related to the prednisone use,” Blocker recalled. But that seemed questionable: He had taken the drug for about eight weeks and not at a high dose.

A year later, after other treatments had failed and Blocker’s hip joints began to collapse, both hips were replaced in operations three months apart.

“I spent 2012 mostly inside,” said Blocker, then a 20-year-old undergraduate who took a year-long medical leave from Mississippi College and moved back home. “It was very difficult.”

Premature failure

Between 2012 and 2016, Blocker said, he again broke his nose and wrist, along with several toes. One night in February 2016 Blocker was sitting on his bed when he turned to grab something off a bedside table. He instantly felt a shooting pain in his hip so intense he was unable to move. His wife, Emily, summoned a friend who carefully scooped Blocker off the bed, carried him to the car, and drove him to a nearby emergency room.

Doctors diagnosed a partially dislocated hip. Blocker was sent home on crutches and told to see an orthopedist, who told him his new hips had failed after less than four years.

“I knew in my gut that something was not right,” he recalled. “It made no sense to me that these had failed when they’re supposed to last for 15-plus years. I thought, ‘I’m going to try to figure it out if nobody else will.’ “

Blocker gathered his medical records from doctors’ offices and hospitals around Jackson and began digging.

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Going back years, he noticed that his level of alkaline phosphatase (ALP), a component of a routine blood chemistry panel, was always extremely low. ALP is an enzyme found primarily in the liver, bones, and digestive system. High levels of ALP can signal cancer, a problem with the liver, or mononucleosis. Low levels may indicate a zinc deficiency, malnutrition, or a rare genetic disease called hypophosphatasia (HPP), which affects roughly 1 in 100,000 people and causes bone and dental problems.

“I realized I fit every symptom,” Blocker said. “I had a moment that felt like clarity. I thought, ‘This could be it.’ “

Hypophosphatasia is an inherited disorder caused by mutations of the ALPL gene that disrupt mineralization, the essential process by which calcium and phosphorous are deposited in developing teeth and bones, making them strong and rigid. There are several forms of the disease, which vary in age of onset. The most severe form occurs prenatally, while the mildest affects only teeth.

The disease is particularly prevalent among Mennonites in Manitoba, a province in Canada, where about 1 in 2,500 babies are born with severe HPP, which is inherited in an autosomal recessive manner: Two copies of the mutated gene, usually one from each parent, are required to cause disease. In such cases, the parents may be carriers who do not show signs of illness. Less severe autosomal dominant forms of HPP result from the inheritance of a defective gene from one parent who also may have the disease.

Blocker took the articles he found to his family physician, who had never heard of HPP. He referred Blocker to a geneticist at the University of Mississippi, whom he saw in July 2017.

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After reviewing Blocker’s medical history, including his bowed legs at birth, numerous fractures, osteoporosis, and history of hip replacements, the specialist ordered genetic testing for HPP.

The results confirmed Blocker’s hypothesis: He had the disease, inherited in an autosomal dominant pattern. Blocker, who was raised by his maternal grandparents, said he doesn’t know which parent passed the gene on to him.

“I was relieved,” he said of the news that something other than clumsiness or bad luck was to blame. “It was nice to be right and not feel like a crazy person and have an answer.”

Connecting with an expert

It quickly became clear to Blocker and his doctors that he would need specialized care out of state. The closest expert, 400 miles north of Jackson, was endocrinologist Kathryn Dahir at Vanderbilt University School of Medicine in Nashville. A specialist in metabolic bone disorders, Dahir treats patients and families affected by HPP from “cradle to grave.”

Blocker saw Dahir in early 2018 and spent two days at Vanderbilt undergoing testing and evaluation at the Center for Bone Biology. He is among a handful of the approximately 100 HPP patients Dahir has treated who have self-diagnosed their disease.

“Aaron is a really smart guy — really medically curious,” she said.

One reason his case may have eluded diagnosis, Dahir said, is that the less severe form from which he suffers — juvenile onset — has only recently been described. “Our understanding of the disease has really evolved over the past decade,” she said.

And there may have been a clinical reason doctors did not follow up on Blocker’s abnormally low ALP levels. Until fairly recently, low levels were not necessarily regarded as clinically significant in contrast to high levels and may not have been flagged. That has changed, she said, and “is just a quantum leap forward.”

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Blocker’s history of Crohn’s disease may have played a role, too. Although there is no known association between HPP and Crohn’s, “it makes the diagnosis more complicated,” Dahir observed. “It’s really tough to have two things that affect you musculoskeletally. It’s hard to figure out what is causing what.”

After jousting with his health insurance company, Blocker was approved to take Strensiq, the only drug approved to treat HPP. Blocker said the medication, which he injects six times per week, costs his insurance company about $1.6 million per year. The drug is designed to replace alkaline phosphatase and improve bone health.

“He was very impaired with no other treatment available,” said Dahir, who sees Blocker two or three times a year. “He’s doing OK, but he continues to have additional surgeries.”

While Blocker’s Crohn’s disease has been in remission for five years, his problems related to HPP have not abated.

So far this year he has undergone four operations on his elbows and teeth and has been told he needs knee replacements. After a surgical incision on his elbow failed to heal last month, Blocker was diagnosed with a MRSA infection, his second in a year. He is receiving potent intravenous antibiotics to treat the resistant bacterial infection.

Blocker is trying to ensure that his nearly 4-year-old son benefits from his hard-won knowledge and experience. “He’s being monitored and as of now he’s perfectly healthy,” Blocker said.

He remains incredulous that doctors did not suggest probing the causes of his numerous fractures, dental problems, and low ALP levels and that it was he — not one of them — who came up with the diagnosis.

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“You wonder where the disconnect is,” Blocker said.

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