Abstract
The increasing availability of treatments and the importance of early intervention have stimulated interest in newborn screening for lysosomal storage diseases. Since 2015, 112,446 newborns in North Eastern Italy have been screened for four lysosomal disorders—mucopolysaccharidosis type I and Pompe, Fabry and Gaucher diseases—using a multiplexed tandem mass spectrometry (MS/MS) assay system. We recalled 138 neonates (0.12%) for collection of a second dried blood spot. Low activity was confirmed in 62 (0.06%), who underwent confirmatory testing. Twenty-five neonates (0.02%) were true positive: eight with Pompe disease; seven with Gaucher disease; eight with Fabry disease; and two with Mucopolysaccharidosis type I. The combined incidence of the four disorders was 1 in 4497 births. Except for Pompe disease, a second-tier test was implemented. We conclude that newborn screening for multiple lysosomal storage diseases combined with a second-tier test can largely eliminate false-positives and achieve rapid diagnosis.
Highlights
Lysosomal storage diseases (LSDs) are inborn errors of metabolism related to lysosome impairment
We report our three-year experience of over 110,000 neonates screened for LSDs and discuss the role of biomarkers as second-tier tests in a newborn LSD screening program
Between September 2015 and February 2019, 112,446 newborns were screened for the four LSDs. 138 neonates (0.12%) had an enzyme activity below 0.2 MOM and were recalled for collection of a second dried blood spots (DBSs) (Table 1)
Summary
Lysosomal storage diseases (LSDs) are inborn errors of metabolism related to lysosome impairment. When LSDs are suspected, biochemical assays demonstrating the accumulation substrate such as lysosphingolipids (LysoGb1 for Gaucher disease, LysoGb3 for Fabry disease, LysoSM and LysoSM509 for Niemann-Pick diseases A/B and C), glycosaminoglycans (GAGs) for MPSs and oligosaccharides for Pompe (tetrasaccharide), enzyme analysis in leukocytes/lymphocytes and gene analysis allow to confirm the diagnosis [1,2].The increasing availability of therapies and the importance of early intervention have stimulated interest in the use of newborn screening (NBS) to diagnose these disorders. The development of fluorimetry coupled with “digital microfluidics” (DMF) and electrospray ionization tandem mass spectrometry (MS/MS) for detecting LSDs allow a simultaneous quantification of several enzymes’ activity [4,5], permitting the neonatal diagnosis of Gaucher, Pompe, Fabry, MPS I, Niemann-Pick type A/B and Krabbe diseases.
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