Application of MALDI-TOF Mass Spectrometry for Non-invasive Diagnostics of Mucopolysaccharidosis IIIA

Abstract

Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disorder (LSD) caused by deficiency of lysosomal N-sulphoglucosamine sulphohydrolase, which is one of four enzymes involved in heparan sulfate degradation. Traditional methods used for MPS IIIA diagnostics usually constitute of selective screening, based on the analysis of urinary glycosaminoglycans, further enzymatic assays in leukocytes, and mutation analysis. Nowadays, some LSDs, including mucopolysaccharidoses, can be precisely diagnosed by mass spectrometry-based techniques. Up to this date, there are no comprehensive studies of MPS IIIA diagnostics by MALDI-TOF analysis of free oligosaccharides in urine published. In the presented work, MALDI-TOF/TOF analysis of permethylated oligosaccharides was performed to obtain the set of glyco-biomarkers that together form the specific fingerprint of this disease. Early and accurate diagnostics of MPS IIIA is crucial to stabilize the progressive cellular damage and improve the overall well-being of patients.

Omics-Based Approaches for the Characterization of Pompe Disease Metabolic Phenotypes

“…Other studies have been focused on evaluating the performance of different analytical methods as metabolic screening tools for different LSDs causing an accumulation of oligosaccharides (OS) [ 105 , 106 , 107 ]. In this line, Semeraro and colleagues evaluated the performance of an ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS/MS) which allowed to characterize the different oligosaccharide species in urine and dried urine spot (DUS) samples in a chromatographic run less than 30 min [ 94 ].…”