Hypophosphatasia

Hypophosphatasia is a rare inherited metabolic bone disease caused by loss-of-function mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase. The resulting enzyme deficiency impairs bone mineralization, leading to skeletal deformities, recurrent fractures, and premature tooth loss. Clinical severity ranges from lethal perinatal forms to milder adult-onset presentations with chronic musculoskeletal pain. Diagnosis depends on persistently low serum alkaline phosphatase levels combined with ALPL genetic testing and radiographic assessment. Enzyme replacement therapy with asfotase alfa has improved skeletal outcomes, particularly in affected children. Early identification by multidisciplinary care teams is essential to prevent respiratory and orthopedic complications.