Rare diseases pose a number of challenges for patients and medical professionals alike, from getting an accurate diagnoses to finding treatment. However for those with hypophosphatasia (HPP), a life-threatening, genetic metabolic bone disease that affects 1 in 100,000 people worldwide, there’s cause for optimism. A growing body of scientific data, effective drug therapies, and greater awareness are giving patients and health care practitioners new hope.

HPP affects patients of all ages, but symptoms can differ greatly depending on age of presentation

Its most severe form may be detected through a prenatal ultrasound, which may show that the skeleton is malformed and under-developed. Such pregnancies may result in stillbirth, while some newborns just days old may die due to respiratory failure.

Infantile HPP may appear within the first six months marked by a failure to grow at the expected rate the baby’s age and gender. A misshapen head could occur because of craniosynostosis, early fusion of the bones of the skull. Soft bones may cause limbs to take on a rickets-like look with deformities of the legs. The risk of death among babies is significant with 31 percent mortality at three months and 58 percent at one year.

Childhood HPP, can manifest through an unusual or waddling gait, developmental delays, “knock knees,” skeletal malformation (around ages two and three), muscle weakness, as well as joint, muscle, bone pain, and fractures. These changes can impact a child’s ability to keep up with their peers.

Adults can experience mobility issues, fractures, and muscle and bone pain. About 23 percent of adults with HPP require the use of a wheelchair and 25 percent need a walking device.

While HPP symptoms can vary widely, there is one common thread. Children with the disease may lose teeth earlier than normal.  Non-traumatic tooth loss with the root still attached before age 5 is an important indicator of HPP. More than 99 percent of HPP patients experience this, making it a crucial clue for making an HPP diagnosis.

Generations impacted by recessive gene disorder

“It runs in families,” explains Dr. Chitra Prasad, the Director of Clinical Metabolic Services at the London Health Sciences Centre in London, ON, “especially among Mennonites living in Manitoba, where the incidence of HPP is one in 2,500. The disease can have a profound effect on patients, with some living with chronic pain, loss of mobility, and significant disabilities.”
HPP can have multi-system implications for patients. They can face kidney damage and failure, respiratory issues, and premature tooth loss. Yet the disease is difficult to diagnose, since its symptoms are similar to those of other diseases like rickets or osteoarthritis. But with more physicians and dentists learning to recognize the telltale signs of the disease, patients are getting answers sooner.

An important diagnostic tool is a blood test for alkaline phosphatase (ALP). Low levels are a hallmark biochemical marker of HPP. Doctors also perform specialized tests (such as examining DNA and urine amino acids) and look at X-rays to spot bone fractures.

“HPP is more readily diagnosed in children,” says Dr. Prasad. “Parents may seek help from their family physician or a pediatrician after noticing problems with a child’s gait or their inability to gain weight. With adults, trouble walking or muscle weakness may prompt them to see a doctor.”

Canada’s leadership role in HPP treatment

In 1948, Canadian physician Dr. John Rathbun was the first to coin the term hypophosphatasia. Since then, Canada has been recognized as the world leader in HPP research and treatments, including drug therapy. Working with health care professionals, patients can manage their pain with non-steroidal anti-inflammatory medications (NSAIDs), and can also focus on tooth loss prevention with good dental care and bone strengthening through doctor-directed exercises.

“The approach to HPP used to be just based on symptomatic treatment,” says Dr. Prasad. “That’s changed with the introduction of a drug that can replace an enzyme that’s deficient in HPP patients.”

With more management options for HPP available, there’s hope that patients can live without debilitating pain and loss of independence due to mobility issues. Canada’s role in making that happen is certainly something we can celebrate.