Fast urinary screening of oligosaccharidoses by MALDI-TOF/TOF mass spectrometry

Laurent Bonesso,Raymond Mengual,Monique Piraud,Charlotte Hinault,Emmanuel Van Obberghen,Céline Caruba

doi:10.1186/1750-1172-9-19

Abstract

BackgroundOligosaccharidoses, which belong to the lysosomal storage diseases, are inherited metabolic disorders due to the absence or the loss of function of one of the enzymes involved in the catabolic pathway of glycoproteins and indirectly of glycosphingolipids. This enzymatic deficiency typically results in the abnormal accumulation of uncompletely degraded oligosaccharides in the urine. Since the clinical features of many of these disorders are not specific for a single enzyme deficiency, unambiguous screening is critical to limit the number of costly enzyme assays which otherwise must be performed.MethodsHere we provide evidence for the advantages of using a MALDI-TOF/TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometric (MS) method for screening oligosaccharidoses. Urine samples from previously diagnosed patients or from unaffected subjects were randomly divided into a training set and a blind testing set. Samples were directly analyzed without prior treatment.ResultsThe characteristic MS and MS/MS molecular profiles obtained allowed us to identify fucosidosis, aspartylglucosaminuria, GM1 gangliosidosis, Sandhoff disease, α-mannosidosis, sialidosis and mucolipidoses type II and III.ConclusionsThis method, which is easily run in less than 30 minutes, is performed in a single step, and is sensitive and specific. Invaluable for clinical chemistry purposes this MALDI-TOF/TOF mass spectrometry procedure is semi-automatizable and suitable for the urinary screening of oligosacharidoses.

Highlights

Oligosaccharidoses, called glycoproteinoses, are inherited metabolic diseases corresponding to a subset of lysosomal storage disorders resulting in deficient activity of one of the lysosomal hydrolases involved in the degradation of oligosaccharide components of glycoproteins
Oligosaccharidoses involve mainly the catabolic pathways for N-linked-glycoprotein breakdown that are bidirectional with sequential cleavages from both the reducing end of the oligosaccharide released after proteolysis, and from the non-reducing end (Additional file 1: Figure S1)
Oligosaccharidoses form a group of metabolic disorders [2] including fucosidosis (α-L-fucosidase deficiency), aspartylglucosaminuria (N-aspartyl-β-glucosaminidase deficiency), sialidosis, GM1 gangliosidosis (β-Dgalactosidase deficiency), Sandhoff disease called GM2 gangliosidosis variant O (N-acetyl-β-D-hexosaminidase deficiency), α-mannosidosis (α-D-mannosidase deficiency) and β-mannosidosis (β-D-mannosidase deficiency)

Summary

Introduction

Oligosaccharidoses, called glycoproteinoses, are inherited metabolic diseases corresponding to a subset of lysosomal storage disorders resulting in deficient activity of one of the lysosomal hydrolases involved in the degradation of oligosaccharide components of glycoproteins. Oligosaccharidoses include mucolipidoses type II and III (ML II and III), resulting from the deficiency of Nacetylglucosaminyl-1-phosphotransferase This enzyme is required to generate a mannose-6-phosphate residue, the absence of which leads to incorrect addressing of hydrolases to the lysosomes [2]. Oligosaccharidoses, which belong to the lysosomal storage diseases, are inherited metabolic disorders due to the absence or the loss of function of one of the enzymes involved in the catabolic pathway of glycoproteins and indirectly of glycosphingolipids. This enzymatic deficiency typically results in the abnormal accumulation of uncompletely degraded oligosaccharides in the urine. Since the clinical features of many of these disorders are not specific for a single enzyme deficiency, unambiguous screening is critical to limit the number of costly enzyme assays which otherwise must be performed

Methods

Results

Conclusion