Comment Because for as long as he can remember, Aaron Blocker’s bones have given him trouble. Born with severely bowed legs, Blocker as a baby wore metal leg braces while sleeping, which allowed him to walk. Even so, he said, his legs “always hurt.” The rash of broken bones started when he was 10 and fell on his hand, breaking several fingers. A few years later he broke his nose for the first time when it was cut, not forcefully, by a soft plastic swing. “My family thought I was a clumsy kid,” said Blocker, 30, who grew up near Jackson, Miss., where he still lives. “I was very active.” Over the years, Blocker said, doctors set his broken bones and treated other orthopedic problems, including scoliosis, a sideways curvature of the spine. But no one 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. She was ambushed by a sharp pain in her leg that hit her without warning The early and unexpected failure of these hip replacements convinced Blocker his skeletal problems had an overlooked cause. At 24, while a graduate student in biomedical research, Blocker took his skills and taught them to himself. He spent several weeks digging through his medical records and browsing scientific websites before hitting dirt: a possible diagnosis that was later confirmed by genetic testing. “It was a relief to have an answer,” said Blocker, who works for an insurance broker. “But I always wondered, how did this get lost for so long?” The answer, one of his doctors later opined, may reflect evolving scientific knowledge about his rare diagnosis, as well as Blocker’s own complicated medical history. Blocker’s bones weren’t his only problem. “I had a lot of problems with my teeth growing up,” she said. His molars, usually the largest and strongest teeth, were inexplicably broken. By the time he graduated high school, seven teeth had been removed. Blocker also had several cavities, which his dentist attributed to “weak teeth.” He had two wisdom teeth removed in high school and healing was unusually slow. the oral surgeon noticed a weakness in his jawbone but did not recommend further investigation. Medical mystery: Back pain plagued her for 30 years. A repeated indication triggered a delayed diagnosis. Halfway through his years, Blocker developed recurring problems with his right shoulder. The first time he dislocated it by throwing a ball. Another dislocation occurred while he was sleeping, although no one could explain how or why this happened. During his senior year of high school, Blocker was forced to deal with a more pressing 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. Chronic inflammatory bowel disease causes severe diarrhea and weight loss. He was prescribed prednisone, a key 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 a disturbing and unexpected incidental finding: avascular necrosis of both hips. A bone density scan also found that Blocker had severe osteoporosis. This woman’s desperate persistence helped spark her lucky break Avascular necrosis occurs when the blood supply to a bone is interrupted, causing the tissue to collapse and die and threatening the integrity of the structure. Causes include long-term steroid use, especially in 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. “The orthopedist told me that the bones in my hip were dying, and he said it could be related to the prednisone use,” Blocker recalled. But that seemed doubtful: He had been on 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’s medical leave from Mississippi College and returned home. “It was very difficult.” Between 2012 and 2016, Blocker said, he broke his nose and wrist again, along with several toes. One night in February 2016, Blocker was sitting up in his bed when he turned to grab something from a nightstand. He immediately felt a pain in his hip so severe that he could not move. His wife, Emily, called a friend who carefully pulled Blocker out of bed, carried him to the car and drove him to a nearby emergency room. Nearly 100 doctors tried to diagnose this man’s devastating disease — without success 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 wrong,” he recalls. “It didn’t make sense to me that these had failed when they were supposed to last for 15-plus years. I thought, “I’ll try to figure it out if no one else does.” “ Blocker gathered his medical records from the doctors’ offices and hospitals around Jackson and started digging. Going back years, he noticed that his alkaline phosphatase (ALP) level, a component of a routine blood chemistry panel, was always extremely low. ALP is an enzyme found mainly in the liver, bones and digestive system. High ALP levels can signal cancer, a liver problem, or mononucleosis. Low levels may indicate zinc deficiency, malnutrition or a rare genetic disease called hypophosphatasia (HPP), which affects about 1 in 100,000 people and causes bone and tooth 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 in the ALPL gene that disrupt mineralization, the key process by which calcium and phosphorus 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 appears prenatally, while the mildest only affects the 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 for causing disease. In such cases the parents may be carriers who show no signs of disease. Less severe autosomal dominant forms of HPP result from inheriting a defective gene from a parent who may also have the disease. Blocker took the articles he found to his family doctor, who had never heard of HPP. He referred Blocker to a geneticist at the University of Mississippi, whom he saw in July 2017. Some doctors don’t like some patients After reviewing Blocker’s medical history, including his bowed legs at birth, multiple fractures, osteoporosis and a 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 crazy and have an answer.”
Connect with an expert It quickly became clear to Blocker and his doctors that he would need specialized care out of state. The nearest specialist, 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 tests and evaluation at the Bone Biology Center. He is among a handful of the roughly 100 HPP patients Dahir has treated who have self-diagnosed the disease. “Aaron is a very smart guy – very medically curious,” he said. One reason his case may have gone undiagnosed, Dahir said, is that the less severe form he suffers from — juvenile onset — has only recently been described. “Our understanding of the disease has really evolved over the last decade,” he said. And there may have been a clinical reason the doctors didn’t follow up on Blocker’s unusually low ALP levels. Until fairly recently, low levels were not necessarily considered clinically significant in contrast to high levels and may not have been noted. That has changed, he said, and “it’s just a quantum leap forward.” Blocker’s history of Crohn’s disease may also have played a role. Although there is no known association between HPP and Crohn’s, “it makes the diagnosis more complicated,” Dahir noted. “It’s really hard to have two things affecting you musculoskeletally. It’s hard to understand what causes what.” After going with his health insurance company, Blocker was approved to take Strensiq, the only drug approved to treat HPP. Blocker said the drug, which he injects six times a week, costs his insurance company about $1.6 million a year. The drug is designed to replace alkaline phosphatase and improve bone…
