Sanfilippo syndrome type C: deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase in skin fibroblasts

Abstract

Removal of N-sulfated glucosamine residues during degradation of heparan sulfate is accomplished by the sequential action of three enzymes. Action of sulfamidase resuits in the formation of α-glucosaminide residues. Removal of these groups requires conversion to α-N-acetylglucosaminide by the action of an acetyltransferase in the presence of acetyl- CoA, followed by hydrolysis by α-N-acetylglucosaminidase. In fibroblast homogenates from three patients with Sanfilippo syndrome type C (mucopolysaccharidosis III C), a biochemical variant of the Sanfilippo syndrome, complete deficiency of the acetylCoA:α-glucosaminide N-acetyltransferase activity was detected. Activities of all lysosomal hydrolases known so far to degrade mucopolysaccharides, including those of sulfamidase and α-N-acetyl lucosaminidase, were in the range of controls. Acetyl-CoA:α-glucosaminide N-acetyltransferase activity was normal in fibroblasts of patients with other genetic mucopolysaccharidoses, including Sanfilippo syndrome A and B.