Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.
Skin fibroblasts from two 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 th sulfatase activities of normal fibroblasts were found. These observations suggest that N-acetylglucosamine-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; we propose that this deficiency causes Sanfilippo disease type D.
D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009083:Mucopolysaccharidoses / Q000201:enzymology*; D009084:Mucopolysaccharidosis III / Q000201:enzymology*; D013429:Sulfatases / Q000172:deficiency* / Q000378:metabolism
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D013429:Sulfatases; C018719:N-acetylglucosamine-6-sulfatase