A clinical and research protocol for characterizing patients with hypophosphatasia.

H ypophosphatasia is a rare inherited disorder characterized by a wide spectrum of defects in mineralized tissues. The disease is usually inherited as an autosomal recessive trait with a prevalence of approximately 1/100,000 live births. 1 The clinical manifestations are highly variable, ranging from an almost total lack of skeletal formation to the premature loss of the permanent anterior teeth. The scarcity of hypophosphatasia patients and the diversity of their symptoms create special challenges for the clinician, who is unlikely to benefit from broad experience with the disease. These difficulties are compounded by basic science researchers who require standardized and thorough clinical descriptions of affected individuals. It is now possible to characterize the precise mutation(s) at the root of this disorder. To successfully relate the underlying biochemical deficit to its clinical sequelae, it is necessary to document the complete range of physical signs and symptoms of the hypophosphatasia patient. We anticipate that the next 5 to 10 years will see tremendous progress in identifying mutations underlying childhood hypophosphatasia. As scientists go on to clone and characterize these mutations, the pediatric dentist must assume an expanded role in diagnosis, clinical description, tissue collection, and referral to appropriate genetics or research institutions. Our objectives in this report are threefold: