Journal Article

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

Giulia Polo, Leonardo Salviati, Vincenza Gragnaniello, Dominique P Germain, Antonella Giuliani, Alessandro P Burlina, Evelina Maines, Giovanni Duro, Chiara Cazzorla, Laura Rubert, Alberto B Burlina

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: [SDV]Life Sciences [q-bio] / alpha-Galactosidase / Birth / Blood & organ donations / Children / Disease / Dried blood spot / Dried Blood Spot Testing / Dried blood spot; Fabry disease; GLA gene; Globotriaosylsphingosine; Lyso-Gb3; Newborn screening; Second tier test; Tandem mass spectrometry; Variant interpretation; α-galactosidase A; Dried Blood Spot Testing; Fabry Disease; Female; Follow-Up Studies; Glycolipids; Humans; Infant, Newborn; Italy; Male; Neonatal Screening; Sphingolipids; Time Factors; alpha-Galactosidase / Enzymes / Fabry disease / Fabry disease; GLA gene; dried blood spot; globotriaosylsphingosine; lyso-Gb3; newborn screening; second tier test; tandem mass spectrometry; variant interpretation; ?-galactosidase A / Fabry's disease / Female / Females / Follow-Up Studies / Genotype & phenotype / GLA gene / globotriaosylsphingosine / Glycolipids / Humans / Infant, Newborn / Italy / Life Sciences / Lymphocytes / Lyso-Gb3 / Lysosomal storage diseases / Male / Males / Medical screening / Microbiology / Neonatal Screening / Neonates / Newborn screening / Patients / Phenotypes / Plasma / QR1-502 / Second tier test / Sphingolipids / Tandem mass spectrometry / Time Factors / Variant interpretation / X chromosomes / α-galactosidase A