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

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

Vincenza Gragnaniello  1 , Alessandro P Burlina  2 , Giulia Polo  1 , Antonella Giuliani  1 , Leonardo Salviati  3 , Giovanni Duro  4 , Chiara Cazzorla  1 , Laura Rubert  1 , Evelina Maines  5 , Dominique P Germain  6 , Alberto B Burlina  1
Affiliations

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

Vincenza Gragnaniello et al. Biomolecules. .

Abstract

Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.5 years of NBS for FD by α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) assays in dried blood spot through a multiplexed MS/MS assay. Furthermore, we report our experience with long-term follow-up of positive subjects. We screened more than 170,000 newborns and 22 males were confirmed to have a GLA gene variant, with an incidence of 1:7879 newborns. All patients were diagnosed with a variant previously associated with the later-onset phenotype of FD or carried an unclassified variant (four patients) or the likely benign p.Ala143Thr variant. All were asymptomatic at the last visit. Although lyso-Gb3 is not considered a reliable second tier test for newborn screening, it can simplify the screening algorithm when its levels are elevated at birth. After birth, plasma lyso-Gb3 is a useful marker for non-invasive monitoring of all positive patients. Our study is the largest reported to date in Europe, and presents data from long-term NBS for FD that reveals the current incidence of FD in northeastern Italy. Our follow-up data describe the early disease course and the trend of plasma lyso-Gb3 during early childhood.

Keywords: Fabry disease; GLA gene; dried blood spot; globotriaosylsphingosine; lyso-Gb3; newborn screening; second tier test; tandem mass spectrometry; variant interpretation; α-galactosidase A.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Trend in plasma lyso-Gb3 levels over time in all subjects positive for Fabry disease. (b) Plasma lyso-Gb3 levels over time in patients carrying later-onset variants. (c) Plasma lyso-Gb3 levels over time in subjects carrying benign and unclassified variants (including p.Ala143Thr). Abbreviation: yrs: years.
Figure 1
Figure 1
(a) Trend in plasma lyso-Gb3 levels over time in all subjects positive for Fabry disease. (b) Plasma lyso-Gb3 levels over time in patients carrying later-onset variants. (c) Plasma lyso-Gb3 levels over time in subjects carrying benign and unclassified variants (including p.Ala143Thr). Abbreviation: yrs: years.
Figure 2
Figure 2
Proposal for a diagnostic algorithm of male newborn screening for Fabry disease. MOM: multiple of median; DBS: dried blood spot.
See this image and copyright information in PMC

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