542 Archives of Disease in Childhood

Since hypophosphatasia was first described (Rathbun, 1948), other cases which have been recognized have raised the possibility that this defect of alkaline phosphatase is an inherited inborn error of metabolism. Schneider and Corcoran (1950) first suggested that this was an inherited disorder when two cases were found in one family, and this was corroborated by Sobel, Clark, Fox and Robinow (1953). McCance, Fairweather, Barrett and Morrison (1956) demonstrated reduced levels of serum alkaline phosphatase in three generations of one family, suggesting that this was a recessively inherited disorder in which the heterozygous state could be demonstrated by measuring the serum alkaline phosphatase or the phosphoethanolamine in the urine of carriers of the trait. Fraser (1957) then reviewed the literature and pointed out that 26% of reported siblings were affected: the expected incidence of a recessive characteristic. Kretchmer, Stone and Bauer (1958) tried unsuccessfully to identify heterozygous carriers by studies of alkaline phosphatase in leucocytes. Most recently, Harris and Robson (1959) have reported a study of 381 relatives of known cases by urinary chromatograms for phosphoethanolamine, demonstrating a manifestation rate of 0 58 with this method. Because of the importance in genetic counselling, it was felt worthwhile to study the family of two cases which have been under observation since 1954 and reported, in part, by Rathbun (1959). The aim of the study was to determine, if possible, the definitive level of serum alkaline phosphatase indicative of the carrier state and the incidence of the carrier state in 30 relatives in three generations.