Hypophosphatasia: Pediatric forms

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP). Pediatricians encounter a perinatal, an infantile and a childhood form of the disease, but in all cases the predominant feature is defective mineralization. Clinical severity and classification generally reflect the age at which rickets develops. Patients with perinatal hypophosphatasia are stillborn or live only a few days. Infantile hypophosphatasia (onset within the first six months) causes dramatically reduced skeletal mineralization and systemic symptoms such as recurrent pneumonia, vomiting, convulsions and muscle weakness. Childhood hypophosphatasia results in rickets and premature loss of teeth. In children with an especially mild form of the disease, the mineralization defect is restricted to the teeth (odontohypophosphatasia). Study of the disease is also contributing significantly to knowledge of the biology of human TNSALP. Skin fibroblasts derived from patients provide an in vitro system for studies of hypophosphatasia.