Implementation of Second-Tier Tests in Newborn Screening for Lysosomal Disorders in North Eastern Italy

Alberto B Burlina; Giulia Polo; Laura Rubert; Daniela Gueraldi; Chiara Cazzorla; Giovanni Duro; Leonardo Salviati; Alessandro P Burlina

doi:10.3390/ijns5020024

Implementation of Second-Tier Tests in Newborn Screening for Lysosomal Disorders in North Eastern Italy

Int J Neonatal Screen. 2019 Jun 21;5(2):24. doi: 10.3390/ijns5020024. eCollection 2019 Jun.

Authors

Alberto B Burlina¹, Giulia Polo¹, Laura Rubert¹, Daniela Gueraldi¹, Chiara Cazzorla¹, Giovanni Duro², Leonardo Salviati^{3

4}, Alessandro P Burlina⁵

Affiliations

¹ Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Children's Health, University Hospital of Padova, Via Orus 2/B, 35129 Padova, Italy.
² Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Via Ugo La Malfa, 153-90146 Palermo, Italy.
³ Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.
⁴ IRP Città della Speranza, Corso Stati Uniti 4, 35129 Padova, Italy.
⁵ Neurological Unit, St. Bassiano Hospital, Via dei Lotti 40, 36061 Bassano del Grappa, Italy.

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.

Keywords: Fabry disease; GAGs; Gaucher disease; MPS I; Pompe disease; biomarkers; lysoGb1; lysoGb3; lysosomal expanded newborn screening; second-tier test.