A congenital deficiency in the enzyme is associated with
X-linked ichthyosis, a scaly-skin disease affecting roughly 1 in every 2,000 to 6,000 males. The excessive
skin scaling and
hyperkeratosis is caused by a lack of breakdown and thus accumulation of cholesterol sulfate, a steroid that stabilizes cell membranes and adds cohesion, in the outer layers of the skin. Both steroid sulfatase deficiency and common genetic risk variants within STS may confer increased
atrial fibrillation risk. Cardiac
arrhythmia in STS deficiency may be related to abnormal development of the
interventricular septum or
interatrial septum. Blood-clotting abnormalities may occur more frequently in males with XLI and female carriers. Knockdown of STS gene expression in human skin cell cultures affects pathways associated with skin function, brain and heart development, and blood-clotting that may be relevant for explaining the skin condition and increased likelihood of ADHD/autism, cardiac arrhythmias and disorders of
hemostasis in XLI. Steroid sulfates like DHEA sulfate and estrone sulfate serve as large biologically inert reservoirs for conversion into androgens and estrogens, respectively, and hence are of significance for
androgen- and
estrogen-dependent conditions like
prostate cancer,
breast cancer,
endometriosis, and others. A number of clinical trials have been performed with inhibitors of the enzyme that have demonstrated clinical benefit, particularly in oncology and so far up to Phase II. The non-steroidal drug
Irosustat has been the most studied to date. ==Inhibitors==