Heterogeneity of adult hypophosphatasia. Report of severe and mild cases.

Two cases of women with adult hypophosphatasia illustrate the clinical spectrum and potential difficulties in the diagnosis of this condition. Both patients had subnormal serum alkaline phosphatase activity, absence of leukocyte alkaline phosphatase, increased amounts of urinary phosphoethanolamine, and normal levels of immunoreactive calcitonin and parathyroid hormone. In undecalcified bone biopsy specimens, the number of osteoblasts and the tetracycline-labeled calcification front were similar in the two patients, although the percentage of unmineralized bone matrix and the extent of osteoid-covered bone surface were different. Twenty years of bone pain, severe skeletal deformities, and a generalized increase of osteoid in one patient contrasted with an 18-month history of bone pain and patchy osteoid in the other. These cases suggest that adult hypophosphatasia is a heterogeneous disorder and may be more common than previously realized.