Synthesis of the endogenous non-reducing end heparan sulfate disaccharide for newborn screening and diagnosis of Mucopolysaccharidosis type IIIA

Abstract

Mucopolysaccharidosis IIIA (MPS IIIA) is caused by deficiency of the lysosomal enzyme heparan N-sulfatase. Newborn screening of MPS IIIA is carried out by first-tier measurement of enzyme activity followed by measurement of accumulated heparan sulfate-derived biomarker, both by tandem mass spectrometry. Here we described the synthesis of the endogenous non-reducing end disaccharide (in unlabeled and heavy isotopic form) that can be used for quantification of this biomarker in patient samples.

Keywords: Diagnosis; Inborn errors of metabolism; Lysosomal storage disease; Mucopolysaccharidosis-III; Newborn screening; Sanfilippo syndrome type A.