DIFFERENCES IN THE NONREDUCING ENDS OF HEPARAN SULFATES EXCRETED BY PATIENTS WITH MUCOPOLYSACCHARIDOSES REVEALED BY BACTERIAL HEPARITINASES- A NEW TOOL FOR STRUCTURAL STUDIES AND DIFFERENTIAL-DIAGNOSIS OF SANFILIPPOS AND HUNTERS SYNDROMES

Enzymatic and chemical analyses of the structures of heparan sulfates excreted in the urine by patients with Sanfilippo's and Hunter's syndr omes revealed that their nonreducing ends differ from each other and r eflect the enzyme deficiency of the syndromes. The heparan sulfates fr om the different syndromes were treated with heparitinase II, crude en zyme extracts from Flavobacterium heparinum, and nitrous acid degradat ion. The heparan sulfates from patients with Sanfilippo A (deficient i n heparan N-sulfatase) and Sanfilippo B (deficient in alpha-N-acetylgl ucosaminidase) were degraded with heparitinase II producing, besides u nsaturated disaccharides, substantial amounts of glucosamine N-sulfate and N-acetylglucosamine, respectively. The heparan sulfate from patie nts with Hunter's syndrome (deficient in iduronate sulfatase) were deg raded by heparitinase II or crude enzyme extracts to several products, including two saturated disaccharides containing a sulfated uronic ac id at their nonreducing ends. The heparan sulfate from patients with S anfilippo's C syndrome (deficient in acetyl Co-A:alpha-glucosaminide a cetyltransferase) produced, by action of heparitinase II, among other products, two sulfated trisaccharides containing glucosamine with a no nsubstituted amino group. In addition to providing a new tool for the differential diagnosis of the mucopolysaccharidoses, these results bri ng new insights into the specificity of the heparitinases from Flavoba cterium heparinum.