Pilot study of newborn screening for six lysosomal diseases in Brazil

Mol Genet Metab. 2023 Jul 13;107654. doi: 10.1016/j.ymgme.2023.107654.

PMID: 37507255

Francyne Kubaski, Ines Sousa, Tatiana Amorim

Highlights: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing.

Abstract

Background: Lysosomal diseases (LDs) are progressive, potentially fatal conditions that frequently present with no symptoms at birth. For many LDs, there are specific treatments available, and early intervention improves patient outcomes. Newborn screening (NBS) is therefore advantageous for various disorders. Six LDs were the subject of a pilot investigation using tandem mass spectrometry that was completed in Brazil.

Methods: Unselected neonates' dried blood spot (DBS) samples were examined using the Neo-LSDTM kit from Perkin-Elmer by MS/MS. Low enzyme activity samples were used in the second-tier ultra-performance liquid chromatography tandem-mass spectrometry evaluation of particular biomarkers and the third-tier next-generation sequencing (NGS) multi-gene panel analysis. The same DBS sample underwent each test.

Results: In the analysis of 20,066 newborns, 15 samples had one enzyme activity below the cutoff. Five newborns exhibited biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA, whereas two newborns had biochemical and molecular results consistent with Fabry disease.

Conclusions: According to this study, using an enzyme assay as a first-tier test resulted in an acceptably low number of positive results, necessitating the employment of a second- or third-tier test. This approach is appropriate to large NBS projects because it allows for the execution of all tests in a DBS sample.

Keywords: Biomarkers, Enzyme analysis, Lysosomal storage diseases, Newborn screening, Tandem mass spectrometry