Newborn screening for lysosomal storage diseases

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2015-02, Vol.61 (2), p.335-346
• Main Authors: Gelb, Michael H, Scott, C Ronald, Turecek, Frantisek
• Format: Article
• Language: English
• Subjects: Disease; Dried Blood Spot Testing - methods; Enzymatic activity; Enzyme Assays - methods; Enzymes; Fatty acids; Fluorometry; Fluorometry - methods; Humans; Immunologic Techniques - methods; Infant, Newborn; Laboratories; LSD; Lysergic acid diethylamide; Lysosomal Storage Diseases - blood; Lysosomal Storage Diseases - diagnosis; Lysosomal Storage Diseases - enzymology; Mass spectrometry; Medical screening; Metabolism; Methods; Molecular weight; Mutation; Neonatal Screening - methods; Proteins; Scientific imaging; Studies; Tandem Mass Spectrometry - methods
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2014.225771

There is worldwide interest in newborn screening for lysosomal storage diseases because of the development of treatment options that give better results when carried out early in life. Screens with high differentiation between affected and nonaffected individuals are critical because of the large number of potential false positives. This review summarizes 3 screening methods: (a) direct assay of enzymatic activities using tandem mass spectrometry or fluorometry, (b) immunocapture-based measurement of lysosomal enzyme abundance, and (c) measurement of biomarkers. Assay performance is compared on the basis of small-scale studies as well as on large-scale pilot studies of mass spectrometric and fluorometric screens. Tandem mass spectrometry and fluorometry techniques for direct assay of lysosomal enzymatic activity in dried blood spots have emerged as the most studied approaches. Comparative mass spectrometry vs fluorometry studies show that the former better differentiates between nonaffected vs affected individuals. This in turn leads to a manageable number of screen positives that can be further evaluated with second-tier methods.