Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA

Glycobiology. 2020 Jul 20;30(7):433-445. doi: 10.1093/glycob/cwz109.


Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N-acetyl-D-galactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N-acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N-acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients.

Keywords: N-acetylgalactosamine-6-sulfatase; biomarker; chondroitin sulfate; mucopolysaccharidosis IVA.

MeSH terms

  • Adult
  • Cells, Cultured
  • Child
  • Chondroitin Sulfates / chemistry
  • Chondroitin Sulfates / metabolism*
  • Chondroitin Sulfates / urine
  • Chondroitinsulfatases / metabolism
  • Enzyme Replacement Therapy
  • Humans
  • Mucopolysaccharidosis IV / metabolism*
  • Mucopolysaccharidosis IV / therapy
  • Mucopolysaccharidosis IV / urine


  • Chondroitin Sulfates
  • Chondroitinsulfatases
  • GALNS protein, human