Hypophosphatasia

Introduction

Hypophosphatasia (HPP) is an autosomal recessive disorder that is characterized by poor mineralization of bones and teeth. There are at least six phenotypes, which are distinguished from each other by age at diagnosis, inheritance pattern, and prognosis. The primary forms are named for age at diagnosis and include perinatal (lethal), infantile, childhood, and adult HPP. In most cases that are diagnosed perinatally, infants are either stillborn or die in the immediate neonatal period from respiratory insufficiency owing to abnormal thorax and pulmonary hypoplasia, although there are cases with nonlethal outcomes. Infantile HPP manifests by 6 months of age and is associated with failure to thrive, premature craniosynostosis, respiratory complications from rickets of the chest, and seizures. Childhood HPP manifests with early loss of deciduous teeth and bone pain. The first sign of the adult form of HPP is often foot pain from stress fractures.

Other, very rare forms are odontohypophosphatasia and pseudohypophosphatasia; the former usually manifests in middle age with loss of adult teeth, and is associated with only dental and biochemical abnormalities, and the latter clinically and radiologically appears the same as the infantile form except serum alkaline phosphatase is normal. This chapter focuses on the perinatal subtype because the diagnosis can be suggested by prenatal ultrasound (US).

Disorder