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. 2025 Apr 25;11(2):31.
doi: 10.3390/ijns11020031.

Expanded Newborn Screening in Italy: The First Report of Lombardy Region

Clarissa Berardo  1   2 , Alessandra Vasco  2 , Alessia Mauri  1   2 , Simona Lucchi  2 , Laura Cappelletti  2 , Laura Saielli  2 , Manuela Rizzetto  2 , Davide Biganzoli  2 , Cristina Montrasio  2 , Diana Postorivo  2 , Elisa Pratiffi  2 , Andrea Meta  2 , Stephana Carelli  1   2 , Alessandro Amorosi  3 , Sabrina Paci  4 , Graziella Cefalo  4 , Francesca Furlan  5 , Francesca Menni  5 , Serena Gasperini  6 , Viola Crescitelli  6 , Giuseppe Banderali  4 , Gianvincenzo Zuccotti  1   7 , Luisella Alberti  2 , Cristina Cereda  2
Affiliations

Expanded Newborn Screening in Italy: The First Report of Lombardy Region

Clarissa Berardo et al. Int J Neonatal Screen. .

Erratum in

Abstract

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016-2020) of the expanded NBS program in the Lombardy region, Italy.

Methods: Dried blood spots were collected from newborns' heels at 48-72 h after birth. FIA-MS/MS was performed to evaluate specific biochemical markers. Genetic confirmation was achieved via Sanger or NGS on newborns and reported to a clinical reference center (CRC).

Results: A total of 343,507 newborns were tested; 1414/343,507 resulted as positive to NBS and were reported to the CRC. A total of 209 newborns were diagnosed with IEMs: 206 infants received a diagnosis of IEM through NBS, confirmed by genetic analysis; three neonates were not positive to NBS but were subsequentially diagnosed with IEMs. A total of 1208/343,507 were false positive cases. Twenty-seven types of IEMs were diagnosed in 209 patients: 111 newborns were affected by aminoacidemias, 11 by urea cycle disorders, 27 by organic acidemias, 34 by fatty acid oxidation disorders, and 26 by secondary conditions.

Conclusions: We report here for the first time the IEM incidence and distribution in the Lombardy region in the first five years of NBS.

Keywords: aminoacidemias (AAs); fatty acid oxidation disorders (FAODs); inborn errors of metabolism (IEMs); mass spectrometry (MS); newborn screening (NBS); organic acidemias (OAs); rare diseases; urea cycle defects (UCDs).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of NBS workflow in Lombardy region (Italy).
Figure 2
Figure 2
IEMs identified in Lombardy population via NBS. The pie chart on the left indicates the percentage of UCDs (yellow), AAs (peach), FAODs (violet), OAs (light blue), and SCs (emerald) determined in our cohort. The pie chart on the right displays the percentage of the different disorders calculated to the total of IEMs.
Figure 3
Figure 3
Distribution of males (violet) to females (orange) of the 27 IEMs identified in our cohort.
Figure 4
Figure 4
Exemplificative false positive cases. DBS biochemical results of the following: (A) acylcarnitines of two twins not mutated in ACADVL gene; (B) acylcarnitines of a newborn with a VUS having 25% of enzymatic activity; (C) DBS (violet) and plasma (blue) levels of citrulline in a newborn with negative genetic analysis. Dotted lines: 99° percentile cut-off referred for each marker.
See this image and copyright information in PMC

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