Hypophosphatasia patients find answers and treatments
The metabolic bone disorder known as hypophosphatasia (HPP) is rare enough that many medical trainees and even practicing physicians have never seen a case. However, doctors at the University of Chicago Medicine have been diagnosing and treating this under-recognized condition for years. Because HPP has wide-ranging symptoms that can overlap with more common disorders, expert insights are essential for avoiding misdiagnosis.
“Many rheumatologists and endocrinologists don’t feel comfortable treating HPP because they haven’t seen enough of it, so patients have the best chance of receiving proper treatment if they find a team of experts or a dedicated center,” said UChicago Medicine Medical Group rheumatologist Keith Reich, DO,* who practices at UChicago Medicine Ingalls Memorial in Flossmoor.
What is hypophosphatasia?
HPP is a genetic disorder caused by mutations that interfere with the production and activity of an enzyme called alkaline phosphatase, which is essential for the proper development and ongoing health of bones and teeth. All HPP patients have low alkaline phosphatase levels, and the disease is generally more severe when less of the enzyme remains active in the body. HPP can affect all ages, and no two cases are the same.
In infants and children, symptoms can include (but are not limited to):
- Softened bones
- Skeletal malformation
- Weakness
- Stunted growth
- Early tooth loss
In adults, symptoms can include (but are not limited to):
- Headaches
- Body aches
- Joint and bone pain
- Joint swelling
- Frequent bone fractures
- Dental issues
- Depression
In some cases, Reich said the disorder causes calcium deposition in the tissues, which can manifest as painful kidney stones or inflammatory arthritis.
Expertise helps prevent misdiagnosis of hypophosphatasia
HPP is underdiagnosed, Reich said, with many patients going without a correct diagnosis or proper treatment for years. Not only is it frustrating and often painful to lack answers or effective symptom management for so long, but incorrectly diagnosed patients are frequently treated with traditional osteoporosis medications, which can actually make HPP worse.
Reich recalled one patient with a particularly frustrating diagnostic odyssey:
“She’d been to a number of physicians before coming to UChicago Medicine, all of whom seemed to think she was crazy or tried to diagnose her with something like fibromyalgia or depression. They never came up with anything. When she came to us, we made a point of listening to her and taking a thorough history, which led us to the correct diagnosis even before we ordered the laboratory tests as final confirmation.”
Experts at UChicago Medicine have been treating patients with HPP for many years — experience that helps them uncover and recognize the disorder quickly. For example, laboratory results sometimes only flag alkaline phosphatase levels as abnormal if they’re too high, but Reich and his team at Ingalls know to keep an eye out for low levels of the enzyme. Similarly, when going over health history, they’ve learned to include seemingly strange questions that can quickly point to an HPP diagnosis.
“It’s surprising how often it turns out that one of my patients says they lost teeth with the root intact as children or had serious dental problems as a teenager,” Reich said. “The clues for HPP diagnosis are there if you know what questions to ask and what to test for.”
Expert treatment for hypophosphatasia
Fortunately, an HPP diagnosis is not a reason to panic. There are now effective treatments that can help patients regain the strength and health needed to accomplish their goals. In 2015, the FDA approved the first drug to offer enzyme replacement for HPP patients’ low alkaline phosphatase levels.
“We’ve seen this treatment be life-changing for these patients,” Reich said. “It's not something that works overnight, but we have seen some dramatic changes over six months to a year. It’s allowed many people to go back to work and have a normal life, and infants born with a severe form of HPP now survive because of this drug when they otherwise wouldn’t. It’s wonderful.”
Alongside enzyme replacement therapy, patients with HPP may benefit from a combination of other treatments like pain management, physical therapy and dietary adjustments to support overall bone health. At UChicago Medicine, teams of specialists in rheumatology, endocrinology and other fields work together to create personalized treatment plans that address each patient’s specific needs. This collaborative approach ensures that all aspects of the patient’s condition are considered, optimizing outcomes and improving long-term quality of life.
Reich said he and other experts at UChicago Medicine Ingalls Memorial hope to eventually open a metabolic bone clinic in Chicago's south suburbs to treat disorders like osteoporosis, hypophosphatemia and hypophosphatasia.
“A dedicated bone clinic will help us better serve the people of our community, as well as the referring physicians who need our help to care for their patients — especially those with complicated cases or rare conditions,” he said.
*Dr. Keith Reich is a UChicago Medicine Medical Group provider. UChicago Medicine Medical Group is comprised of UCM Medical Group, Inc. f/k/a UCM Care Network Medical Group, Inc., and UCM Medical Group, LLC f/k/a Primary Healthcare Associates, UChicago Medicine at Ingalls - Flossmoor or UChicago Medicine at Ingalls Memorial.