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Newborn screening for Pompe disease in Italy: Long-term results and future challenges

Authors :
Vincenza Gragnaniello
Pim W.W.M. Pijnappel
Alessandro P. Burlina
Stijn L.M. In 't Groen
Daniela Gueraldi
Chiara Cazzorla
Evelina Maines
Giulia Polo
Leonardo Salviati
Giovanni Di Salvo
Alberto B. Burlina
Source :
Molecular Genetics and Metabolism Reports, Vol 33, Iss , Pp 100929- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

Pompe disease (PD) is a progressive neuromuscular disorder caused by a lysosomal acid α-glucosidase (GAA) deficiency. Enzymatic replacement therapy is available, but early diagnosis by newborn screening (NBS) is essential for early treatment and better outcomes, especially with more severe forms. We present results from 7 years of NBS for PD and the management of infantile-onset (IOPD) and late-onset (LOPD) patients, during which we sought candidate predictive parameters of phenotype severity at baseline and during follow-up. We used a tandem mass spectrometry assay for α-glucosidase activity to screen 206,741 newborns and identified 39 positive neonates (0.019%). Eleven had two pathogenic variants of the GAA gene (3 IOPD, 8 LOPD); six carried variants of uncertain significance (VUS). IOPD patients were treated promptly and had good outcomes. LOPD and infants with VUS were followed; all were asymptomatic at the last visit (mean age 3.4 years, range 0.5–5.5). Urinary glucose tetrasaccharide was a useful and biomarker for rapidly differentiating IOPD from LOPD and monitoring response to therapy during follow-up. Our study, the largest reported to date in Europe, presents data from longstanding NBS for PD, revealing an incidence in North East Italy of 1/18,795 (IOPD 1/68,914; LOPD 1/25,843), and the absence of mortality in IOPD treated from birth. In LOPD, rigorous long-term follow-up is needed to evaluate the best time to start therapy. The high pseudodeficiency frequency, ethical issues with early LOPD diagnosis, and difficulty predicting phenotypes based on biochemical parameters and genotypes, especially in LOPD, need further study.

Details

Language :
English
ISSN :
22144269
Volume :
33
Issue :
100929-
Database :
Directory of Open Access Journals
Journal :
Molecular Genetics and Metabolism Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.7db341a8b0d04471852e409a9183746c
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ymgmr.2022.100929