Diagnosis is made based on HPP signs and symptoms, using a combination of blood tests, bone and dental exams, and medical history. No single test can confirm HPP on its own, because symptoms can vary widely from person to person. Doctors need to look at all the results together to “connect the dots”. In Canada, diagnosis can be confirmed by genetic testing. 

Doctors specializing in HPP, such as metabolic bone experts in Canada, are familiar with HPP and more likely to recognize it and make the correct diagnosis. However, many physicians are not familiar with the condition. As a result, HPP is often mistaken for other diseases at first, which can delay the correct diagnosis. In babies and children, diagnosis is made on average about 12 months after symptoms first appear. In adults, where symptoms are usually milder, correct diagnosis can be delayed on average by about 10 years. Repeated fractures in adults may be mistaken for osteoporosis, and joint pain and swelling may be mistaken for gout.

A key sign of HPP is a consistently low ALP in the blood, which can be measured in a routine blood panel in Canada. In many bone conditions, ALP levels are high, so low blood ALP can be an important clue. However, low ALP can also occur in other conditions, so it cannot confirm HPP on its own. It is also important that labs use reference ALP ranges that are specific to men, women and different age categories to avoid incorrect diagnosis. For example, normal ALP activity is lower in adults than in children and if a child’s result is compared to an adult reference range, it may be incorrectly concluded that it is normal.

Another helpful diagnostic blood test measures PLP, the main form of vitamin B6 in the blood. This test can be ordered by any doctor in Canada. In HPP, PLP levels are high because ALP normally helps break down PLP. When ALP activity is low, PLP builds up in the blood.

While other blood tests may also be done by some doctors, they are generally not readily available in Canada (such as PPi) or are less reliable for diagnosing HPP (such as PEA or phosphoethanolamine). Therefore, the combination of low ALP and high PLP on blood tests should be a strong clue for diagnosing HPP. Even so, these blood test results alone are not enough, and other types of tests are still needed.

X-rays can show bone deformities typical of HPP, especially in babies and children with more severe forms. However, these signs can be mistaken for other conditions, if HPP is not already suspected. Knowing what to look for—especially when blood tests suggest HPP—can help doctors make the correct diagnosis. X-rays can also be used to identify fractures.

Dental history is also important, and doctors may ask when and how teeth were lost. Medical history related to bones, joints, and muscles can also be helpful, because children or adults may experience muscle weakness, joint pain or swelling, and fractures.

Genetic testing can look for mutations in the ALPL gene and is ordered by HPP specialists in Canada to confirm HPP diagnosis. If done early, it can potentially reduce the risk of misdiagnosis and speed up the correct diagnosis of HPP.

Outside of supporting diagnosis, genetic testing can also help show how HPP was inherited and whether other family members may be affected. However, it cannot predict how severe the disease will be, because even people with the same mutation in the ALPL gene can have different symptoms.

Genetic testing can look for mutations in the ALPL gene and is ordered by HPP specialists in Canada to confirm HPP diagnosis. If done early, it can potentially reduce the risk of misdiagnosis and speed up the correct diagnosis of HPP.

Outside of supporting diagnosis, genetic testing can also help show how HPP was inherited and whether other family members may be affected. However, it cannot predict how severe the disease will be, because even people with the same mutation in the ALPL gene can have different symptoms.