Boosting Awareness of This Rare Genetic Condition Can Save Lives

Dr. Leanne Ward

Medical Director, CHEO Genetic and Metabolic Bone Disease Clinic & Scientific Director, Ottawa Pediatric Bone Health Research Group

Jennifer Paulson

Director, Soft Bones Canada

Increasing awareness of hypophosphatasia is essential for supporting Canadians living with this rare condition, along with their caregivers and doctors.

Hypophosphatasia (HPP) is a rare genetic disease that’s caused by a lack of alkaline phosphatase, an enzyme that’s important for skeletal mineralization — for making bones hard, essentially. While the disease has a wide spectrum of presentations and the severity varies from patient to patient, its symptoms are often life-altering and, at times, fatal. Therefore, raising awareness about the disease is important as it can help to prevent diagnostic delays, decrease the burden of disease on HPP patients through effective treatment, and ultimately provide a better quality of life for those affected by the condition.

Understanding HPP 

“The lay term for HPP is ‘soft bones,’” says Dr. Leanne Ward, Medical Director of the CHEO Genetic and Metabolic Bone Disease Clinic and Scientific Director of the Ottawa Pediatric Bone Health Research Group. “With the alkaline phosphatase deficiency, patients indeed have soft bones, which results in bone pain, poor growth in children, X-ray findings that look like rickets, premature loss of teeth with the root intact, and a whole host of other medical conditions that go along with the condition.”

The features and symptoms of HPP depend on its severity. “Infants with a severe form of HPP have respiratory issues and may have other problems like seizures, failure to thrive, and striking X-ray findings, with the bones looking poorly mineralized and the growth plates appearing similar to rickets,” says Dr. Ward. In less severe cases, patients may not be diagnosed until childhood or even adulthood. “In these cases, the classic presentation would be bone pain, poor growth in children, dental issues, problems walking and running, fatigue, and often deformity of the limbs and fractures,” notes Dr. Ward. Knowing what to look for can help patients get a quicker diagnosis and faster access to treatment.

The challenges of diagnosis 

Diagnostic delays often arise with HPP because the condition is so rare, and so there’s a lack of general awareness. Therefore, educating health-care practitioners on the signs and symptoms to watch for is critical.

For Jennifer Boin, a 50-year-old guidance counsellor and mother of two who lives in St. Thomas, Ont., her HPP diagnosis came early — around the age of two, after a dentist first noticed her unusual tooth loss — but “no one understood what it was, and there was no real follow-up because it didn’t seem to be affecting my long bones,” she relates. “Then, in my 20s, I started getting a lot of muscle and joint pain, and no one could explain why.” Boin researched independently and began connecting the dots, which led to her being re-diagnosed with HPP in 2013.

Boin’s journey to diagnosis included genetic testing and then family screening to see where her HPP had come from. “Unexpectedly, it turned out that both my parents had given me a bad gene,” she says. “There’s no history of HPP in my dad’s family as far as we know.”

In my 20s, I started getting a lot of muscle and joint pain, and no one could explain why.

Jennifer Boin

Genetic testing and family screening

“This condition has different modes of inheritance,” notes Dr. Ward. “It can be inherited from a family member, or it can occur because of what’s called a ‘de novo pathogenic variant’ — when the variant has never occurred in the family before but occurs in an individual for the very first time — so the diagnosis is ultimately made based on genetic testing. Sometimes family members have HPP but their symptoms are so mild or so non-specific (like pain and lack of stamina) that they go undiagnosed for decades.” 

Besides looking for the physical signs and symptoms of HPP along with testing for a low alkaline phosphatase level in the blood (which many children’s hospitals in Canada now “red flag” when there is a low value, helping to improve time to diagnosis), genetic testing of the ALPL gene is part of the diagnostic process. It’s important in the interpretation of alkaline phosphatase levels to know that they vary with the age and sex of an individual. Physicians have to make sure, for example, that a child’s alkaline phosphatase level is benchmarked to pediatric normal ranges, and not to adult values.

Even with a conclusive diagnosis in hand, HPP patients face many challenges. Not only do they have to deal with the symptoms of HPP — which include loss of teeth, bone pain and deformity, poor growth, fractures, and challenges that go beyond dental and skeletal issues — but they must also find subspecialists who understand their condition. 

Sometimes family members have HPP but their symptoms are so mild or so non-specific (like pain and lack of stamina) that they go undiagnosed for decades.

The burden of disease

“Because HPP has a multi-system effect, treatment requires multiple specialties,” says Dr. Ward. “Management of the disease and all its comorbidities is complex and quite challenging for both patients and physicians.” 

To manage her HPP, Boin does yoga, sees a massage therapist and osteopath, and takes pain medication. She’s also on enzyme replacement therapy, the only HPP treatment currently available in Canada, but notes that accessing the treatment was a challenge. HPP can also be a burden financially, as Boin notes that the cost of her dental work and treatments — such as physiotherapy and massage — aren’t covered.

We connect, empower, and educate patients and caregivers in the Canadian HPP community.

Soft Bones Canada helps HPP patients navigate these challenges. “We connect, empower, and educate patients and caregivers in the Canadian HPP community,” says Jennifer Paulson, one of the volunteer-based organization’s directors. “We do our best to provide whatever information and support our patients need.” From educational initiatives to patient gatherings to help accessing treatment, Soft Bones Canada aims to lessen the burden of HPP — because living with a rare condition isn’t easy, and we all have work to do when it comes to understanding and treating them.

This article was made possible with financial support from Alexion Pharma Canada. The views and opinions expressed in this article do not necessarily reflect the views or positions of Alexion.