Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives

• Published in: International Journal of Neonatal Screening
• Main Authors: Adelaide Ambrosio, Tiziana Fioretti, Barbara D’Andrea, Lucia Pezone, Ilaria Bitetti, Carmela Di Domenico, Sabrina Vallone, Valeria Maiolo, Angela Cioce, Mariano Giustino, Antonio Varone, Gabriella Esposito
• Format: Article
• Language: English
• Published: MDPI AG 2025-08-01
• Subjects: spinal muscular atrophy; newborn screening; carrier screening; targeted therapy
• Online Access: https://www.mdpi.com/2409-515X/11/3/64

Three targeted therapies are currently available for spinal muscular atrophy (SMA), which have dramatically changed the natural history of this severe and potentially fatal disease. More than 95% of SMA cases have a homozygous deletion of exon 7 of the <i>SMN1</i> gene. Disease expression mainly depends on the copy number of <i>SMN2</i>, a hypomorphic copy of <i>SMN1</i>. Many countries in the world have implemented newborn screening (NBS) programs for early identification and treatment of children with SMA. We herein present the first two-year results of the SMA NBS program in Campania, a region with one of the highest birth rates in Italy. Genomic DNA was extracted from dried blood spots (DBS) and peripheral blood. For DBS, the <i>SMN1</i> gene copy number was evaluated by quantitative polymerase chain reaction (qPCR) targeting <i>SMN1</i> exon 7 and a reference gene (<i>RPP30</i>). In positive newborns and their parents, <i>SMN1</i>/<i>SMN2</i> copies were evaluated by multiplex ligation probe amplification (MLPA). We analyzed 77,945 newborns and identified 11 positive children. Six patients had 2 copies of <i>SMN2</i>, but only one showed severe SMA-related signs at birth. Eligible newborns were treated with gene therapy within 20 days of birth. Notably, qPCR failed to amplify the reference <i>RPP30</i> gene in 10/77,945 DBS. Despite this limitation, we observed that about 1/40 DBS had ΔCt values consistent with the presence of one <i>SMN1</i> copy. The semi-automated procedure used for SMA NBS showed excellent performance in detecting the presence of homozygous deletion of <i>SMN1</i> exon 7, with the exception of a few cases with the absence of amplification of the reference gene. By solving this limitation, the screening procedure has the potential to detect heterozygous carriers of the <i>SMN1</i> deletion and, consequently, identify families at procreative risk of SMA.