A comprehensive and targeted next-generation sequencing (NGS) approach may help reduce delays in diagnosing lysosomal storage diseases (LSDs) including lysosomal acid lipase deficiency (LAL-D) and Pompe disease, according to a new article by Italian researchers.

Published in the journal Gene, the article showed that a targeted NGS-based panel was able to identify a reference group of 26 samples with high accuracy (98.4%), sensitivity (95.2%), and specificity (97.6%).

The study authors proposed the use of the NGS-based panel as “a useful second-tier diagnostic test for specialists in everyday clinical management who might suspect an LSD, given its ability to provide accurate and timely information.”

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The Matthews Correlation Coefficient, which can measure the correlation between observed and predicted classifications of samples, yielded a value of 0.964 for the NGS-based approach.

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“NGS technology is currently offering the opportunity to improve the LSD diagnostic workflow, given its low cost, semi-automated pipeline, short processing time, and ability to simultaneously detect multiple nucleotide variants on several genes,” the authors suggested.

“The use of targeted NGS may represent a real and valuable strategy for providing timely and correct diagnoses, for detecting carriership status, and for ensuring genetic counseling for family planning.”

The LSD panel was created using published and available information of 65 genes implicated in LSDs. The complete panel covered 237.782 kb and includes 1241 amplicons that range in size from 125-275 bp.

The panel was tested against a set of 26 standard samples obtained from the Coriell Institute Biobank. The NGS workflow found 40 correctly called true-positive variants, 83 true negatives, and 2 false negatives using single-gene analysis.

“Molecular profiling and genomic sequencing information may prompt the design of novel therapeutic drugs targeting specific mutations, thus opening the possibility for personalized medicine,” the authors concluded.

“Efforts in this sense may prompt patient-oriented outcomes, may improve the quality of life of patients and their families, and may reduce both direct and indirect costs (e.g., caregivers’ services) to national health services and families.”


La Cognata V, Cavallaro S. A comprehensive, targeted NGS approach to assessing molecular diagnosis of lysosomal storage diseases. Genes. 2021;12(11):1750. doi:10.3390/genes12111750