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Toward newborn screening of metachromatic leukodystrophy: results from analysis of over 27,000 newborn dried blood spots. | LitMetric

AI Article Synopsis

Article Abstract

Purpose: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns.

Methods: To minimize the false-positive rate, a two-tier screening algorithm was designed. The primary test was to quantify C16:0-sulfatide in DBS by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The screening cutoff was established based on the results from 15 MLD newborns to achieve 100% sensitivity. The secondary test was to measure the ARSA activity in DBS from newborns with abnormal C16:0-sulfatide levels. Only newborns that displayed both abnormal C16:0-sulfatide abundance and ARSA activity were considered screen positives.

Results: A total of 27,335 newborns were screened using this two-tier algorithm, and 2 high-risk cases were identified. ARSA gene sequencing identified these two high-risk subjects to be a MLD-affected patient and a heterozygote.

Conclusion: Our study demonstrates that newborn screening for MLD is highly feasible in a real-world scenario with near 100% assay specificity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395749PMC
http://dx.doi.org/10.1038/s41436-020-01017-5DOI Listing

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