Six different clinical forms of HPP have been described. Prenatal benign hypophosphatasia involves prenatal skeletal manifestations that slowly resolve to become the milder childhood or adult form. Perinatal lethal hypophosphatasia involves significant hypomineralization and leads to hypercalcemia and respiratory insufficiency. Infantile hypophosphatasia is characterized by rickets developing between birth and six months of age. Childhood-onset hypophosphatasia ranges from low bone mineral density with unexplained fractures to rickets. Adult hypophosphatasia involves early loss of adult dentition and stress fractures of the lower extremities in middle age. Lastly, odontohypophosphatasia includes premature exfoliation of primary teeth and/or severe dental caries. Rare cases of infantile hypophosphatasia that have normal serum alkaline phosphatase activity are known as ''pseudohypophosphatasia''.
More than 250 different mutations in the ALPL gene (1p36.12) are known to cause hypophosphatasia. The gene encodes alkaline phosphatase, tissue-nonspecific isozyme (TNSALP) involved in skeletal mineralization.
