Ichthyosis: The Skin Manifestation of Multiple Sulfatase Deficiency

Abstract

Juvenile sulfatidosis (Austin type) or multiple sulfatase deficiency is an extremely rare autosomal recessive disorder affecting the activity of many sulfatases: arylsulfatase A, several mucopolysaccharide sulfatases, and steroid sulfatase. Certain aspects of the clinical phenotype can be attributed mainly to a deficiency of one specific sulfatase. Most patients develop metachromatic leukodystrophy caused by arylsulfatase A deficiency, dysostosis multiplex by mucopolysaccharide sulfatase deficiency, and ichthyotic skin by steroid sulfatase deficiency. We describe a 7-year-old boy with developmental delay from 7 months of age, progressive spastic quadriparesis, and coarse facial features. By 27 months of age, an ichthyotic rash had developed on the limbs, trunk, and scalp. A skin biopsy specimen revealed hyperkeratosis with a normal granular layer. The diagnosis of multiple sulfatase deficiency was demonstrated by measuring sulfatase activities in fresh leukocytes: there were large deficiencies of arylsulfatase A and B plus reduced arylsulfatase C. The ichthyosis associated with multiple sulfatase deficiency has an autosomal recessive inheritance, is caused by steroid sulfatase deficiency, and the scaling is sometimes milder than in X-linked recessive ichthyosis. This could reflect the residual activity of steroid sulfatase in some cases.

Mild ichthyosis in a 4-year-old boy with multiple sulphatase deficiency

“…The boy we report had a more marked reduction in the activity of arylsulphatase A than in that of steroid sulphatase, and this may explain the marked neurological deterioration and the relatively mild skin manifestation. The ichthyotic skin changes in patients with isolated X‐linked steroid sulphatase deficiency are in general more severe than those seen in patients with MSD, possibly reflecting residual activity of steroid sulphatase in MSD 5 . The boy we describe showed no clinical signs of a mucopolysaccharidosis.…”

“…MSD is an extremely rare, autosomal recessive disorder affecting the activity of many sulphatases, including arylsulphatase A, several mucopolysaccharide sulphatases and steroid sulphatase 5 . Fewer than 50 cases have been reported in the literature 5 . MSD was first described by Austin et al 6 .…”

“…Patients may present with symptoms that are attributable to a deficiency in any of these sulphatases. Thus, deficiency in arylsulphatase A causes metachromatic leucodystrophy, deficiency of sulphatases involved in mucopolysaccharide degradation causes dysostosis multiplex and steroid sulphatase deficiency causes ichthyotic skin 5 …”

Inherited ichthyosis: Syndromic forms

“…Multiple sulfatase deficiency (MSD) is rare. Since Austin reported this disease in 1965, 50 or fewer patients were reported before 1997 …”

“…Since Austin reported this disease in 1965, 50 or fewer patients were reported before 1997. 21,22 Etiology/pathological physiology Cholesterol sulfate plays an important role in the adhesion of keratinocytes in the substratum corneum. It exists as a cell membrane component of keratinocytes, and is negatively charged, attracting calcium ions and leading to the calciummediated adhesion of keratinocytes.…”