LAUSR

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 and chondroitin sulfate. The chondroitin sulfate that accumulates in MPS IVA patients has a disease-specific non-reducing end terminating with N-Acetyl-D-galactosamine 6-sulfate which can be specifically quantified after enzymatic depolymerization of chondroitin sulfate polysaccharide chains. The abundance of N-Acetyl-D-galactosamine 6-sulfate over other possible non-reducing end 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 keratan sulfate assay by quantifying chondroitin sulfate-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 chondroitin sulfate derived substrate to manage disease in MPS IVA patients.