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

Area of Science:

• Genetics and Genomics
• Neurology
• Public Health

Background:

• Spinal muscular atrophy (SMA) is a severe genetic disease primarily caused by homozygous deletion of the SMN1 gene.
• The severity of SMA correlates with the copy number of the SMN2 gene.
• Newborn screening (NBS) programs are crucial for early diagnosis and treatment of SMA.

Purpose of the Study:

• To present the initial two-year results of the SMA NBS program in Campania, Italy.
• To evaluate the performance of a semi-automated screening procedure for SMA.
• To assess the potential for identifying SMA carriers and families at risk.

Main Methods:

• Genomic DNA was extracted from dried blood spots (DBS) and peripheral blood of 77,945 newborns.
• Quantitative polymerase chain reaction (qPCR) was used to evaluate SMN1 gene copy number.
• Multiplex ligation probe amplification (MLPA) was employed for SMN1/SMN2 copy number analysis in positive cases and parents.

Main Results:

• Eleven infants with SMA were identified.
• Six patients had two copies of SMN2, with one exhibiting severe symptoms at birth.
• qPCR failed to amplify the reference RPP30 gene in 10 samples, indicating a limitation.

Conclusions:

• The SMA NBS program demonstrated high performance in detecting homozygous SMN1 exon 7 deletions.
• Early treatment with gene therapy was initiated within 20 days for eligible newborns.
• Addressing the reference gene amplification issue could enable carrier detection and risk assessment for families.