Iduronate sulfatase activity in serum, lymphocytes, and fibroblasts--simplified diagnosis of the Hunter syndrome.

A previously described assay for iduronate sulfatase has been adapted for use with serum, lymphocytes, and fibroblasts. The assay also gives a rough measure of iduronidase activity. We have evaluated the procedure for the diagnosis of the Hunter syndrome, for the detection of Hunter heterozygotes, and for the diagnosis of certain other disorders (mucolipidoses II and III and mucopolysaccharidosis I). Hunter patients had 1-2% normal iduronate sulfatase activity in the three sources tested. The serum assay is undoubtedly the method of choice to establish the diagnosis of the Hunter syndrome. Less that 1 ml serum and 3-4 days are required to complete the procedure. Serum could not be used for the detection of iduronidase deficiency diseases, but these could easily be recognized in lymphocyte and fibroblast preparations. The iduronate sulfatase activity of sera from patients with mucolipidoses II and III was elevated 20-fold, but their parents had a normal level of the enzyme. In fibroblasts of patients with mucolipidoses II and III, both iduronate sulfatase and iduronidase activities were markedly decreased. Serum assays were not informative about the Hunter heterozygote status. However, the mean activity in lymphocytes from mothers of Hunter patients was about half of the mean normal activity. A number of obligate heterozygotes had iduronate sulfatase activity so low that they were identifiable as carriers; others, unfortunately, had a clearly normal level. The possibility of carrier detection by the lymphocyte assay needs further development.