A new biochemical subtype of the Sanfilippo syndrome: characterization of the storage material in cultured fibroblasts of Sanfilippo C patients.
Fibroblasts cultured from the skin of three unrelated patients with the clinical symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated intracellularly excessive amounts of heparan sulfate and showed a lengthened turnover time for this mucopolysaccharide. They exhibited, however, neither a deficiency of heparan sulfate sulfamidase or alpha-N-acetylglucosaminidase nor of any other known glycosaminoglycan-degrading hydrolase. This new mucopolysaccharidosis was therefore designated as type C of the Sanfilippo syndrome. The abnormal heparan sulfate metabolism of Sanfilippo C fibroblasts could not be normalized by addition of crude urinary proteins or concentrated secretions from normal fibroblasts to the culture medium or by cocultivation with normal fibroblasts. The accumulated heparan sulfate was characterized by a reduced negative net charge. A small proportion of it could be adsorbed onto a cation exchange resin. It was sensitive to nitrous acid degradation under conditions where glucosamine residues with free amino groups are attacked. It is therefore suggested that the primary defect in this new mucopolysaccharidosis concerns the step which follows the hydrolysis of N-sulfonate groups in heparan sulfate degradation.
D000293:Adolescent; D000328:Adult; D005347:Fibroblasts / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008297:Male; D009083:Mucopolysaccharidoses / Q000378:metabolism*; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism
D005944:Glucosamine; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D013431:Sulfates