Validation of a heparan sulfate-derived disaccharide as a marker of accumulation in murine mucopolysaccharidosis type IIIA

Barbara King, Peter Savas, Maria Fuller, John Hopwood, Kim Hemsley

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28 Citations (Scopus)


Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative lysosomal storage disorder resulting from sulfamidase deficiency, which leads to accumulation of heparan sulfate within lysosomes. We have determined the time-course of accumulation of a disaccharide [hexosamine-N-sulfate[α-1,4] hexuronic acid; HNS-UA] marker of heparan sulfate storage within the brain, liver, and spleen of a naturally occurring mouse model of MPS IIIA. HNS-UA is detectable in the brain of affected mice on the day of birth, when it is significantly increased compared to normal control mice. As mice age, this compound steadily accumulates until a plateau is reached at ∼20-weeks. A similar rate of accumulation of HNS-UA is seen in the liver and spleen of affected mice. Intracerebral delivery of recombinant human sulfamidase reduced the amount of HNS-UA present in segments of the brain receiving the correcting enzyme, thus demonstrating the effectiveness of enzyme replacement therapy within the central nervous system of affected mice. This finding therefore provides evidence for the use of the disaccharide HNS-UA to monitor the effect of therapies for this condition in humans, when treatment strategies are devised.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number2
Publication statusPublished - Feb 2006


  • Electrospray-ionization tandem mass spectrometry
  • Heparan sulfate
  • Lysosomal storage disorder
  • Mouse
  • Mucopolysaccharidosis type IIIA
  • Oligosaccharides
  • Sulfamidase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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