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.

OBJECTIVES:

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.

MAIN OUTCOME MEASURES:

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: An C M Jansen, Henian Cao, Paige Kaplan, Kenneth Silver, Gabriel Leonard, Linda De Meirleir, Willy Lissens, Inge Liebaers, Martin Veilleux, Frederick Andermann, Robert A Hegele, Eva Andermann
• Journal: Archives of neurology (Arch Neurol) Vol. 64 Issue 11 Pg. 1629-34 (Nov 2007) ISSN: 0003-9942 [Print] United States
• PMID: 17998446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamine
• Aspartic Acid
• Sulfatases
• N-acetylglucosamine-6-sulfatase
• Glycine

Topics

• Adolescent
• Adult
• Aspartic Acid (genetics)
• DNA Mutational Analysis
• Disease Progression
• Family Health
• Female
• Glutamine (genetics)
• Glycine (genetics)
• Humans
• Male
• Mucopolysaccharidosis III (genetics, pathology, physiopathology)
• Mutation
• Sulfatases (genetics)