Defective SGSH does not hydrolyse Heparan sulfate chain(7)

Stable Identifier
Reaction [transition]
Homo sapiens
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MPS IIIA (Sanfilippo syndrome A, mucopolysaccharidosis IIIA, MIM:252900) is a rare, autosomal recessive lysosomal storage disease. A deficiency of the enzyme N-sulphoglucosamine sulphohydrolase (SGSH, MIM:605270), which normally hydrolyses the sulfate group from the terminal N-sulphoglucosamine residue of heparan sulfate (HS) leads to the build up of HS in cells and tissues, characterised by severe CNS degeneration in early childhood leading to death between 10 and 20 years of age.
Four mutations (R74C, R245H, S66W, and 1091delC) are known to be prevalent in Polish (Bunge et al. 1997), Dutch (Weber et al. 1997), Italian (Di Natale et al. 1998), and Spanish (Montfort et al. 1998) populations, respectively. These mutations abolish the activity of SGSH being associated with the classic severe phenotype.
Literature References
PubMed ID Title Journal Year
9401012 Identification of 16 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A)

Zaremba, J, Hopwood, JJ, Weber, B, Ince, H, Van Diggelen, OP, Steglich, C, Bunge, S, Beck, M, Gal, A, Kleijer, WJ

Hum Mutat 1997
9285796 Novel mutations in Sanfilippo A syndrome: implications for enzyme function

Weber, B, Bunge, S, Guo, XH, Hopwood, JJ, Cooper, A, Kleijer, WJ, Wraith, JE

Hum Mol Genet 1997
9744479 Mutation 1091delC is highly prevalent in Spanish Sanfilippo syndrome type A patients

Chabás, A, Guidi, S, Coll, MJ, Garcia-Giralt, N, Vilageliu, L, Montfort, M, Grinberg, D

Hum Mutat 1998
9554748 Identification of molecular defects in Italian Sanfilippo A patients including 13 novel mutations

Villani, GR, Esposito, S, Balzano, N, Di Natale, P

Hum Mutat 1998
Catalyst Activity

N-sulfoglucosamine sulfohydrolase activity of SGSH mutants [lysosomal lumen]

Normal reaction
Functional status

Loss of function of SGSH mutants [lysosomal lumen]

Name Identifier Synonyms
mucopolysaccharidosis III DOID:12801 Sanfilippo's syndrome, SANFILIPPO SYNDROME B, N-sulphoglucosamine sulphohydrolase deficiency, Sanfilippo's syndrome, mucopolysaccharidosis type IIIB, NAGLU DEFICIENCY, mucopolysaccharidosis type IIIA, Mucopolysaccharidosis, MPS-III, Mucopolysaccharidosis, MPS-III-B (disorder), mucopolysaccharidosis III, SANFILIPPO SYNDROME A, N-ACETYL-ALPHA-D-GLUCOSAMINIDASE DEFICIENCY, HEPARAN SULFATE SULFATASE DEFICIENCY, mucopolysaccharidosis type III
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