Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by mutations in the ALPL gene, which affects the production of an enzyme called tissue non-specific alkaline phosphatase (TNSALP). This enzyme is essential for bone mineralization, so a deficiency leads to improper bone and tooth development. HPP varies widely in severity, with symptoms ranging from life-threatening skeletal deformities in infants to milder forms that may only cause dental issues in adults.
The disease is typically classified into several types based on the age of onset and symptom severity: perinatal, infantile, childhood, adult, and odonto-HPP (primarily affecting teeth). Common symptoms include bone pain, fractures, premature tooth loss, and, in severe cases, respiratory complications due to chest deformities. Laboratory findings often reveal low levels of alkaline phosphatase (ALP) in the blood.
Management of hypophosphatasia involves supportive care, physical therapy, and sometimes orthopedic surgery. Enzyme replacement therapy, such as asfotase alfa, has shown effectiveness in improving outcomes for severe cases, particularly in infants. Genetic counseling is recommended for affected families due to the hereditary nature of the disease. Although no cure exists, ongoing research and therapies provide hope for improved quality of life for patients with HPP.