Ethanolamine phosphate excretion in a family with hypophosphatasia.

Hypophosphatasia is an inherited disorder of bone, which is thought to be transmitted by a recessive gene. The homozygous form of the disease presents with a well-defined clinical picture and two biochemical abnormalities: lowered serum alkaline phosphatase and excessive urinary excretion of ethanolamine phosphate (EAP). Heterozygous carriers are usually not manifest clinically, but it has been suggested that they may be recognized biochemically. Both serum alkaline phosphatase and urinary EAP excretion have been studied for this purpose. Rathbun, MacDonald, Robinson and Wanklin (1961) studied changes in serum alkaline phosphatase in 30 relatives of two sibs with hypophosphatasia. Of the relatives, 15 (50%) had serum alkaline phosphatase levels below 20 Bodansky units, which was significantly lower than the mean of a comparable group of normal people. About 15% of the normal control group, however, were also below this value. This considerable overlap as well as the great variation in methods of measurement employed in different laboratories greatly reduces the usefulness of this test for the recognition of heterozygotes. Paper chromatography was used by Harris and Robson (1959) to study the urinary excretion of EAP in 381 relatives of 16 cases of hypophosphatasia. This method suffers in this instance from lack of sensitivity, and they were only able to demonstrate EAP excretion in 58% of the expected carriers. The purpose of this paper is to describe the use of ion-exchange chromatography for the accurate measurement of EAP excretion in the immediate members of a family in which two sibs have hypophosphatasia. The clinical aspects of these two cases have been previously described in detail (Bethune and Dent, 1960).