Newborn Screening for 5q Spinal Muscular Atrophy: Comparisons between Real-Time PCR Methodologies and Cost...

Area of Science:

• Genetics and Molecular Biology
• Neonatal Screening
• Public Health

Background:

• Modifying therapies for Spinal Muscular Atrophy (SMA) necessitate reliable newborn screening methods.
• Existing protocols for screening *SMN1* gene deletion lack comparative cost-analysis for implementation in new centers.
• There is a need for cost-effective and accurate diagnostic approaches for SMA in neonatal contexts.

Purpose of the Study:

• To compare qualitative real-time PCR methodologies for *SMN1* deletion screening in neonates.
• To estimate the implementation costs associated with different SMA screening protocols.
• To provide a decision-making framework for centers establishing SMA newborn screening.

Main Methods:

• Comparative analysis of qualitative real-time PCR approaches: presence/absence (P/A) and melt curve.
• Validation using MLPA as a confirmatory test on Brazilian blood samples (dried blood spots - DBS).
• Cost analysis including consumables (simplex and multiplex assays) and equipment acquisition.

Main Results:

• Both P/A and melt curve real-time PCR protocols demonstrated 100% accuracy and concordance.
• Consumable costs per reaction ranged from USD 1.68 to $4.42 (simplex) and USD 2.04 to $12.76 (multiplex).
• Equipment acquisition costs varied significantly, from USD 44,817.07 to $467,253.10.

Conclusions:

• Real-time PCR offers accurate and potentially cost-effective methods for SMA newborn screening.
• The study provides essential data on assay costs and implementation factors for establishing SMA NBS programs.
• This work serves as a foundational step towards implementing SMA newborn screening pilot programs globally.