Urinary excretion of sulphated N-acetylhexosamines in patients with various mucopolysaccharidoses.

Sulphated N-acetylhexosamines have been isolated from human urine and tentatively identified as N-acetylglucosamine 6-sulphate (GlcNAc6S), N-acetylgalactosamine 6-sulphate (GalNAc6S), N-acetylgalactosamine 4-sulphate (GalNAc4S) and N-acetylgalactosamine 4,6-disulphate (GalNAc4,6diS). Urine from mucopolysaccharidosis-Type-IIID, -IVA and -VI patients compared with that from normal individuals contains elevated levels of GlcNAc6S (380-fold), GalNAc6S (180-fold) and GalNAc4S (420-fold) respectively. Urine from mucopolysaccharidosis-Type-VI patients also contain more than 600 times the normal level of GalNAc4,6diS. Urine from a mucolipidosis-Type-II and a multiple-sulphatase-deficient patient, and, in general, all mucopolysaccharidosis patients studied, contain at least 5-10-fold elevations of sulphated N-acetylhexosamines over the levels detected in urine from normal controls and a alpha-mannosidosis patient. Urine from patients with clinically mild phenotypes contains less sulphated N-acetylhexosamines than isolated from urine of clinically severe mucopolysaccharidosis patients. The source of the four sulphated N-acetylhexosamines is not known. However, incubation of a series of oligosaccharide substrates, derived from keratan sulphate and chondroitin 6-sulphate and containing non-reducing-end beta-linked 6-sulphated N-acetylhexosamine residues, with homogenates of cultured human skin fibroblasts has indirectly been shown to release GlcNA6S and GalNAc6S respectively. Release of GalNAc4S could not be demonstrated in similar incubations of oligosaccharide substrates derived from chondroitin 4-sulphate and containing non-reducing-end beta-linked GalNAc4S residues. We propose that some, if not all, of the sulphated N-acetylhexosamine present in human urine is derived from the action of beta-N-acetylhexosaminidase on sulphated GlcNAc or GalNAc residues at the non-reducing end of keratan sulphate, dermatan sulphate or chondroitin sulphate.