Table 1.

Examples of application of novel technologies for LSDs.

Technology	Applications	Examples of successful applications
Genomic sequencing	Diagnosis of LSD patients and identification of mutations of known genes Identification of mutations in genes not associated with LSD	Identification of new LSDs caused by mutation of the VPS33A (Pavlova et al, 2019) and VPS16 (Steel et al, 2020) genes
Transcriptomic analysis	Information on pathways involved in disease pathophysiology Response to environmental conditions /pharmacological manipulations	Similarities between the microglia expression profiles of LSDs (mucolipidosis type IV mouse and Niemann‐Pick disease type C1) with common neurodegenerative disorders (Cougnoux et al, 2019)
Genome‐wide association studies	Identification of modifying factors Information on disease pathophysiology	Identification of a c.510C > T variant that may be predictive of clinical course and outcome in late‐onset Pompe disease patients (Bergsma et al, 2019)
microRNA sequencing	Identification of disease biomarkers that correlate with disease severity and assist in monitoring disease progression and efficacy of therapies Identification of pathways involved in disease pathophysiology	Identification of differentially expressed microRNAs potentially predictive of disease severity in Pompe disease (Tarallo et al, 2019)
Biochemical and metabolomic analyses	Support and validation of diagnosis Identification of disease biomarkers that correlate with disease severity, monitoring disease progression, monitoring efficacy of therapies Newborn screening Identification of pathways involved in disease pathophysiology	Identification of disease biomarkers for several LSDs (Boutin & Auray‐Blais, 2015; Reunert et al, 2015; Polo et al, 2019) Development of methods for simultaneous detection of multiple enzyme activities in dried blood spots suitable for newborn screening programs for several LSDs (Anderson, 2018; Donati et al, 2018; Kumar et al, 2019; Lukacs et al, 2019; Scott et al, 2020)
Cell‐based assays and high‐content imaging technologies	Identification of pathways involved in disease pathophysiology Screening for correctors and therapeutic agents	Development of multiplex staining assays that allow screening of FDA‐approved compounds and identification of correctors for cellular phenotypes of LSDs (Pipalia et al, 2006; Pugach et al, 2018)
Targeted gene knock‐out and genome editing—iPSc	Identification of pathways involved in disease pathophysiology Screening and validation of therapeutic agents Gene editing of mutant genes to correct disease‐causing mutations	CRISPR‐Cas9‐mediated generation of knock‐out models of LSDs, such as sphingolipidoses and Niemann‐Pick disease type C (Santos & Amaral, 2019)
Organellar omics	Information on lysosome biology Identification of pathways involved in disease pathophysiology Identification of disease biomarkers for correlations with disease severity, monitoring disease progression, monitoring efficacy of therapies	Identification of lysosomal proteome and interactome (Sleat et al, 2005; Abu‐Remaileh et al, 2017; Thelen et al, 2017; Rabanal‐Ruiz & Korolchuk, 2018)