Benign familial hyperphosphatasemia

Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific (liver/bone/kidney), demonstrated markedly increased intestinal alkaline phosphatase levels (29% to 44% of total) in all family members and significantly elevated liver/bone/kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests.