Hypophosphatasia (HPP) is a rare, inherited metabolic bone disease that affects the bones and teeth. It is caused by mutations in the gene encoding tissue non-specific alkaline phosphatase (TNSALP), an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including mineralization-inhibiting inorganic pyrophosphate (PPi) and pyridoxal 5’-phosphate (PLP), a major form of vitamin B. When TSNALP enzymatic activity is low, inorganic pyrophosphate (PPi) accumulates outside of cells in the extracellular matrix of bones and teeth, and inhibits formation of hydroxyapatite mineral, the main hardening component of bone, causing rickets in infants and children and osteomalacia (soft bones) and odontomalacia (soft teeth) in children and adults. HPP has remarkably wide-ranging severity, and the six major clinical forms are separated based primarily upon the age when symptoms occur and the diagnosis is made. These forms are perinatal, infantile, childhood (severe or mild), adult, and odontohypophosphatasia. HPP can be diagnosed by measuring the blood level of the form of vitamin B6 called pyridoxal 5ʹ-phosphate (PLP), which is normally broken down by TNSALP. However, this test isn’t widely available and can be expensive. Doctors can often diagnose HPP with other tests, such as abnormal enzyme levels during a routine blood test.