As a result of defects in the development of the dental cementum, the deciduous teeth (baby teeth) are often lost before the age of 5. Frequently, the incisors are lost first; occasionally all of the teeth are lost prematurely. Dental radiographs can show the enlarged pulp chambers and root canals that are characteristic of rickets.Patients may experience delayed walking, a characteristic waddling gait, stiffness and pain, and muscle weakness (especially in the thighs) consistent with nonprogressive myopathy. Typically, radiographs show defects in calcification and characteristic bony defects near the ends of major long bones. Growth retardation, frequent fractures, and low bone density (osteopenia) are common. In severely-affected infants and young children, cranial bones can fuse prematurely, despite the appearance of open fontanels on radiographic studies. The illusion of open fontanels results from hypomineralization of large areas of the calvarium. Premature bony fusion of the cranial sutures may elevate intracranial pressure. Adult hypophosphatasia
Adult hypophosphatasia can be associated with rickets, premature loss of deciduous teeth, or early loss of adult dentation followed by relatively good health. Osteomalacia results in painful feet due to poor healing of metatarsal stress fractures. Discomfort in the thighs or hips due to femoral pseudofractures can be distinguished from other types of osteomalacia by their location in the lateral cortices of the femora.
Although several clinical sub-types of the disease have been characterized, based on the age at which skeletal lesions are discovered, the disease is best understood as a single continuous spectrum of severity.As the presentation of adult disease is highly variable, incorrect or missed diagnosis may occur. In one study, 19% of patients diagnosed with fibromyalgia had laboratory findings suggestive of possible hypophosphatasia.One case report details a 35-year old female with low serum ALP and mild pains but no history of rickets, fractures or dental problems. Subsequent evaluation showed osteopenia and renal microcalcifications and an elevation of PEA. The genetic mutations found in this case were previously reported in perinatal, infantile and childhood hypophosphatasia, but not adult hypophosphatasia. Perinatal hypophosphatasia
Perinatal hypophosphatasia is the most lethal form. Profound hypomineralization results in caput membranaceum (a soft calvarium), deformed or shortened limbs during gestation and at birth, and rapid death due to respiratory failure. Stillbirth is not uncommon and long-term survival is rare. Neonates who manage to survive suffer increasing respiratory compromise due to softening of the bones (osteomalacia) and underdeveloped lungs (hypoplastic). Ultimately, this leads to respiratory failure. Epilepsy (seizures) can occur and can prove lethal. Regions of developing, unmineralized bone (osteoid) may expand and encroach on the marrow space, resulting in myelophthisic anemia.In radiographic examinations, perinatal hypophosphatasia can be distinguished from even the most severe forms of osteogenesis imperfecta and congenital dwarfism. Some stillborn skeletons show almost no mineralization; others have marked undermineralization and severe osteomalacia.