Diagnostics of lysosomal storage diseases by mass spectrometry: a review

Lysosomal storage disorders (LSD) are a group of over 70 rare inherited metabolic disorders that are caused mostly by the deficiency of specific lysosomal enzymes. Lack of these enzymes leads to the interference with cellular functions due to excessive accumulation of undegraded substrate in cells and tissues. Effective treatment of these diseases, if it is available, relies on early and accurate diagnostics. Several traditional methods for diagnostics of LSD are used worldwide; however, new techniques, methods and instruments need to be applied to the diagnostic process to increase its sensitivity, repeatability and reliability. In this review, diagnostic methods based on mass spectrometry and their respective sample preparation steps and eventual separation by liquid chromatography are discussed, emphasizing specific biomarkers of each lysosomal storage disorder subclass. Up-to-date evaluation of research conducted in the areas of diagnostics of lysosomal storage disorders by mass spectrometry is comprehensively summarized in this study.