Steroid sulphatase deficiency: identification of heterozygotes using hydrolysis of dehydroepiandrosterone sulphate by peripheral leucocytes

Diagnosis of X-linked recessive ichthyosis, which is expressed only in males, can readily be made by measurement of leucocyte steroid sulphatase activity. However, because the gene for steroid sulphatase activity partly escapes from the process of X-chromosome inactivation associated with gene dosage compensation, identification of heterozygotes (females) is more difficult. We have measured the steroid sulphatase (by hydrolysis of dehydroepiandrosterone sulphate) and beta-glucuronidase (by hydrolysis of methylumbelliferyl glucuronide) activities in leucocytes from 18 heterozygotes, 100 normal females, 100 normal males and 11 affected subjects. When the ratio of the activities of steroid sulphatase and beta-glucuronidase in mixed leucocytes was plotted as a function of the steroid sulphatase activity, 85% heterozygotes were distinguished from normal females. Measurement of steroid sulphatase activity alone with these cells enabled identification of 78% heterozygotes. Measurements on mononuclear leucocytes were much less effective. Thrombocytes showed 1% of the steroid sulphatase activity of leucocytes. In females, leucocyte steroid sulphatase activity was independent of the stage of the ovarian cycle at which the cells were collected.