Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Abstract

Skin fibroblasts from 2 patients who had symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated excessive amounts of heparan sulfate and were unable to release sulfate from N-acetylglucosamine-6-sulfate linkages in heparan sulfate-derived oligosaccharides. Keratan sulfate-derived oligosaccharides bearing the same residue at the nonreducing end and p-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-.beta.-D-glucopyranoside were degraded normally. Kinetic differences between the sulfatase activities of normal fibroblasts were found. N-acetyl-glucosamine-6-sulfate sulfatase activities degrading heparan sulfate and keratan sulfate, respectively, can be distinguished. It is the activity directed toward heparan sulfate that is deficient in these patients; this deficiency apparently causes Sanfilippo disease type D.