Distribution of heparan sulfate oligosaccharides in murine mucopolysaccharidosis type IIIA

Kerryn Mason, Peter Meikle, John Hopwood, Maria Fuller

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Heparan sulfate (HS) catabolism begins with endo-degradation of the polysaccharide to smaller HS oligosaccharides, followed by the sequential action of exo-enzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In mucopolysaccharidosis type IIIA (MPS IIIA) the exo-enzyme, N-sulfoglucosamine sulfohydrolase, is deficient resulting in an inability to hydrolyze non-reducing end glucosamine N-sulfate esters. Consequently, partially degraded HS oligosaccharides with non-reducing end glucosamine sulfate esters accumulate. We investigated the distribution of these HS oligosaccharides in tissues of a mouse model of MPS IIIA using high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Oligosaccharide levels were compared to total uronic acid (UA), which was used as a measure of total glycosaminoglycan. Ten oligosaccharides, ranging in size from di- to hexasaccharides, were present in all the tissues examined including brain, spleen, lung, heart, liver, kidney and urine. However, the relative levels varied up to 10-fold, suggesting different levels of HS turnover and storage. The relationship between the di- and tetrasaccharides and total UA was tissue specific with spleen and kidney showing a different disaccharide:total UA ratio than the other tissues. The hexasaccharides showed a stronger correlation with total UA in all tissue types suggesting that hexasaccharides may more accurately reflect the storage burden in these tissues.

Original languageEnglish
Pages (from-to)1088-1100
Number of pages13
Issue number4
Publication statusPublished or Issued - 11 Dec 2014


  • Electrospray ionization-tandem mass spectrometry
  • Heparan sulfate
  • Lysosomal storage disorder
  • Mouse model
  • Mucopolysaccharidosis type IIIA
  • Oligosaccharides
  • Reverse phase high performance liquid chromatography

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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