699 INCREASED CHOLESTEROL SULFATE IN PLASMA AND RED BLOOD CELL MEMBRANES OF STEROID SULFATASE (STS) DEFICIENT PATIENTS

Abstract

STS deficiency is an inborn error of metabolism due to a relatively common mutation on the short arm of the X chromosome. The phenotype of affected individuals includes decreased estriol production during fetal life and ichthyosis postnatally. Although increased levels of several steroid sulfates have been observed in amniotic fluid, maternal urine, and cord blood from such pregnancies, no consistent substrate abnormalities have been found beyond the perinatal period. Specifically, normal radioimmunoassayable plasma pregnenolone sulfate (PS), dehydroepiandrosterone sulfate (DS), and androstenediol sulfate (AS) have been reported. Utilizing gas chromatography (GC), we have found cholesterol sulfate (CS) to be strikingly elevated in plasma and red blood cell membranes of patients with STS deficiency. 80% methanol extracts were purified by solvent partition and TLC, subjected to solvolysis and quantitated by GC. Recoveries were monitored with 3H-CS. High levels of CS with normal levels of PS, DHEAS, and AS may indicate that desulfation is quantitatively more important for CS than for the other steroid sulfates. CS is known to affect membrane stability and the present observations may help to explain the pathogenesis of STS deficiency and X-linked ichthyosis.