Hypophosphatasia is a rare inherited disease that prevents the body from properly making an enzyme called tissue nonspecific alkaline phosphatase (ALP). Low activity of ALP leads to abnormal bones and teeth.

HPP is caused by mutation(s) in the ALPL gene (also known as the TNSALP gene). This gene provides instructions for making the ALP enzyme. Enzymes are proteins that help chemical reactions happen in the body. ALP supports important body functions, including helping produce phosphate, which is needed to build strong bones and teeth. ALP also helps break down vitamin B6, which supports the action of chemical messengers in the brain (called neurotransmitters).

HPP affects the bones and teeth, because it interferes with a process called mineralization. Mineralization is needed to build strong, hard bones and teeth that stay firmly anchored. People with HPP tend have soft bones, which can lead to deformities or fractures. This is known as rickets, when it affects growing bones in children, or osteomalacia when it affects bones that are no longer growing. Teeth may also become loosely anchored, which can lead to early tooth loss. When HPP appears before or soon after birth, it can cause other serious complications.

HPP symptoms can vary widely from person to person, but a key sign of HPP is a consistently low ALP activity in the blood.

HPP is caused by mutation(s) in the ALPL gene. This gene provides instructions for the body to make an enzyme called tissue-nonspecific ALP. ALP is normally abundant in bones. People with HPP have low ALP activity, which can be measured with a blood test.

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. 

There is currently no cure for HPP. However, enzyme replacement therapy is available in Canada for people who have a confirmed diagnosis of HPP that began in infancy or childhood.