Activity of the microsomal
enzyme,
steroid sulfatase, is absent in keratinocytes, fibroblasts, and leukocytes of patients with recessive
x-linked ichthyosis. This study was undertaken to determine if
cholesterol sulfate, a substrate of this
enzyme, accumulates in the pathological scale of these patients. Scales from 8 patients with recessive
x-linked ichthyosis, 10 patients with other forms of
ichthyosis, and normal human outer stratum corneum were extracted with
chloroform/water (1:2:0.8 by vol) and
lipids were fractionated by quantitative, sequential thin-layer chromatography.
Cholesterol sulfate was identified by cochromatography in several
solvent systems, by its staining characteristics, by biochemical analysis, and by mass spectrometry. The mean
cholesterol sulfate content of recessive x-linked ichthyotic scale was 12.5 +/- 0.8% of the total
lipid, a fivefold increase over normal (P less than 0.0025), whereas the
cholesterol sulfate content of other ichthyotic scale was normal. This increase in
cholesterol sulfate content was accompanied by a decrease in total neutral
lipids (P less than 0.0025) and free
sterols (P less than 0.025) but no change in
sterol esters or total
sterols. These results demonstrate that deficiency of
steroid sulfatase in recessive
x-linked ichthyosis results in excessive accumulation of a substrate,
cholesterol sulfate, in the pathologic scale, which may underly the pathogenesis of the scaling in this disorder. Measurement of
cholesterol sulfate content in scale provides an alternative method to enzymatic assay for the diagnosis of this form of
ichthyosis.