Adult hypophosphatasia; dominant inheritance in a large kindred

Hypophosphatasia, a metabolic bone disease, has arbitrarily been classified as occurring in three forms - 'infantile', 'childhood' and 'adult'. Each is characterized by subnormal circulating activity of alkaline phosphatase (AP), defective bone mineralization resulting in an excess of unmineralized bone matrix (osteoid), and increased urinary excretion of both phosphoethanolamine (PEA) and pyrophosphate. Whereas inheritance of both the infantile and childhood forms is believed to be recessive, the pattern of transmission in the rarely reported adult form is unclear. We wish to report the clinical, laboratory, and genetic investigation of a kindred in which the proposita had all of the features of the adult form of hypophosphatasia.