Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

Marlies J. Valstar, Aida M. Bertoli-Avella, Marja W. Wessels, George J G Ruijter, Bianca De Graaf, Renske Olmer, Peter Elfferich, Sanne Neijs, Roxana Kariminejad, Fatih Suheyl Ezgü, Aysegul Tokatli, Barbara Czartoryska, Ad N. Bosschaart, Feikje Van Den Bos-Terpstra, Hugues Puissant, Friederike Bürger, Heymut Omran, D. Eckert, Mirella Filocamo, Emil SimeonovPatrick J. Willems, Ron A. Wevers, Martinus F. Niermeijer, Dicky J J Halley, Ben J H M Poorthuis, Otto P. Van Diggelen

Research output: Contribution to journalArticlepeer-review


Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 inframe small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

Original languageEnglish
JournalHuman Mutation
Issue number5
Publication statusPublished - May 2010


  • α-N-acetylglucosamine- 6-sulphate sulphatase
  • α-N-acetylglucosamine-6-sulphatase
  • GNS
  • Mucopolysaccharidosis IIID
  • Mutations
  • Sanfilippo syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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