Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Biomolecules 2021 Jun 27;11(7):951. doi: 10.3390/biom11070951.

PMID: 34199132

Vincenza Gragnaniello, Alessandro P Burlina, Giulia Polo

Highlights: This study is the largest reported to date in Europe and presents data from long-term NBS for Fabry disease (FD) that reveals the current incidence of FD in northeastern Italy.

Abstract

Background: Fabry disease (FD) is a multisystemic lysosomal storage disorder that progresses over time. Early detection through newborn screening (NBS) may allow for prompt treatment, sparing irreversible organ damage in the future.

Methods: Using a multiplexed MS/MS assay, we provide the findings of 5.5 years of NBS for FD using α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) tests in dried blood spots. We also provide our findings from long-term follow-up of positive participants.

Results: We tested almost 170,000 newborns, and 22 boys with a GLA gene variant were confirmed, with an incidence of 1:7879 newborns. All of the patients had a mutation previously linked to the FD phenotype with later onset, or had an unclassified variant (four patients) or the presumably benign p.Ala143Thr variant. At the time of the last visit, they were all asymptomatic. Although lyso-Gb3 is not regarded a credible second-tier test for newborn screening, when its levels are raised at birth, it helps simplify the screening algorithm. Plasma lyso-Gb3 is a valuable non-invasive test for all positive patients after delivery.

Conclusion: Our research is the largest in Europe to date, and it uses data from long-term NBS for FD to identify the current FD incidence in northeastern Italy. The early disease course and trend of plasma lyso-Gb3 during early childhood are described in our follow-up data.

Keywords: Fabry disease, GLA gene, dried blood spot, globotriaosylsphingosine, lyso-Gb3, newborn screening, tandem mass spectrometry, α-galactosidase A