title: Sanfilippo syndrome type D: natural history and identification of 3 novel mutations in the GNS Gene.
abstract: BACKGROUND
  Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase (GNS) gene, leading to impaired degradation of heparan sulfate.
  
  
  OBJECTIVE
  To report the natural history of MPS-IIID in 2 siblings described by Kaplan and Wolfe in 1987 and to study the phenotype in 2 other unrelated families with MPS-IIID. Design, Setting, and Patients Case series of 4 patients with MPS-IIID: 2 siblings followed up at the Montreal Neurological Hospital and Institute, 1 patient followed up at the UZ Brussel, and 1 patient recruited through the prenatal counseling program at the UZ Brussel.
  
  
  METHODS
  Clinical and molecular data collected from 3 families with enzyme-based diagnosis of MPS-IIID.
  
  
  RESULTS
  The course of the disease was characteristic of MPS-IIID in all patients, although survival may be longer than was previously reported. In family 1, both siblings were homozygous for a novel nonsense mutation in the GNS gene (c.1168C>T). In family 2, the proband carried a heterozygous mutation occurring in a splice recognition site in the intron 7 boundary (c.876-2A>G). The second mutation in this patient remains to be identified. In family 3, the proband was homozygous for a novel frameshift mutation in GNS due to the insertion of 5 nucleotides (c.1138_1139insGTCCT).
  
  
  CONCLUSIONS
  Major issues in the care of patients with MPS-IIID include behavioral problems, sleep problems, recurrent infections, dysphagia, and pain from orthopedic complications. To date, all mutations in GNS predict protein truncation, and there is no obvious genotype-phenotype correlation.
authors.affiliation: Department of Pediatric Neurology, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. anna.jansen@uzbrussel.be
authors.forename: An C M
authors.initials: AC
authors.lastname: Jansen
authors.forename: Henian
authors.initials: H
authors.lastname: Cao
authors.forename: Paige
authors.initials: P
authors.lastname: Kaplan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Silver
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leonard
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Inge
authors.initials: I
authors.lastname: Liebaers
authors.forename: Martin
authors.initials: M
authors.lastname: Veilleux
authors.forename: Frederick
authors.initials: F
authors.lastname: Andermann
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Eva
authors.initials: E
authors.lastname: Andermann
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005192:Family Health; D005260:Female; D005973:Glutamine / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D009084:Mucopolysaccharidosis III / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D013429:Sulfatases / Q000235:genetics*
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D013429:Sulfatases; C018719:N-acetylglucosamine-6-sulfatase; D005998:Glycine