Biomarkers for Lysosomal Storage Disorders with an Emphasis on Mass Spectrometry

Abstract

Lysosomal storage disorders (LSDs) are characterized by an accumulation of various substances, such as sphingolipids, mucopolysaccharides, and oligosaccharides. The LSD enzymes responsible for the catabolism are active at acidic pH in the lysosomal compartment. In addition to the classically established lysosomal degradation biochemistry, recent data have suggested that lysosome plays a key role in the autophagy where the fusion of autophagosome and lysosome facilitates the degradation of amino acids. A failure in the lysosomal function leads to a variety of manifestations, including neurovisceral disorders. While affected individuals appear to be normal at birth, they gradually become symptomatic in childhood. Biomarkers for each condition have been well-documented and their proper selection helps to perform accurate clinical diagnoses. Based on the natural history of disorders, it is now evident that the existing treatment becomes most effective when initiated during presymptomatic period. Neonatal screening provides such a platform for inborn error of metabolism in general and is now expanding to LSDs as well. These are implemented in some areas and countries, including Taiwan and the U.S. In this short review, we will discuss several issues on some selected biomarkers for LSDs involving Fabry, Niemann–Pick disease type C, mucopolysaccharidosis, and oligosaccharidosis, with a focus on mass spectrometry application to biomarker discovery and detection.

A new UHPLC-MS/MS method for the screening of urinary oligosaccharides expands the detection of storage disorders

“…The diagnosis of storage disorders is often challenging due the presence of common clinical features and great variability in symptoms, and requires a complex approach which includes the analysis of target biomarkers in biological fluids, the measurement of enzymatic activities in leukocytes and/or fibroblasts and the confirmatory diagnosis by mutation analysis [ 20 ]. The availability of novel and specific therapies for a large number of diseases, including oligosaccharidoses, has increased the medical demand of reliable diagnostic techniques to offer precise and timely diagnosis.…”

Lipid Nanoparticles: A Novel Gene Delivery Technique for Clinical Application

“…Lysosomal storage disorders (LSDs) are characterized by an accumulation of unprocessed biochemicals in the lysosome involving 50–60 enzymes [ 57 , 58 , 59 ]. These disorders present CNS, skeletal, and visceral disorders such as hepatomegaly and splenomegaly.…”

Therapeutic Strategies For Tay-Sachs Disease

“…Specifically, both MS technologies can be used to identify proteomic and metabolomic targets for various LSD therapies ( Parenti et al, 2021 ). There is a history of using MS technology to identify biomarkers for LSDs including Fabry disease, Niemann-Pick disease Type C, MSP, and oligosaccharidosis ( Mashima et al, 2020 ). However, there is little evidence of performing a phenotypic screen for an LSD using MS technology.…”