Spinal Muscular Atrophy Newborn Screening Status
Yes, spinal muscular atrophy (SMA) is now part of standard state newborn screening panels in the United States, having been added to the Recommended Uniform Screening Panel in July 2018. As of June 2021,34 states had fully implemented SMA screening, with at least 8 additional states pursuing implementation 1. By February 2024, all 50 U.S. states have achieved full implementation 2.
Historical Context and Rationale for Addition
SMA was added to the Recommended Uniform Screening Panel by the HHS Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) in July 2018, primarily based on the availability and efficacy of newly approved disease-modifying therapies 3, 4.
The original 2006 ACMG uniform screening panel identified 29 core conditions for mandatory screening, but SMA was not included at that time 5.
The approval of nusinersen by the FDA in December 2016 fundamentally changed the treatment landscape, making early identification through newborn screening clinically actionable and beneficial for patient outcomes 4.
Current Implementation and Screening Methodology
State programs utilize real-time quantitative PCR assays on dried blood spots to detect deletions of exon 7 in the survival motor neuron 1 (SMN1) gene 3, 6.
The CDC developed a locked nucleic acid probe-based real-time PCR assay to achieve the necessary specificity for detecting SMN1 exon 7 deletions 2.
The CDC has established comprehensive laboratory support infrastructure, including quality assurance materials, proficiency testing programs supporting 115 newborn screening laboratories worldwide, and external quality control material programs 2.
Clinical Outcomes from Early Implementation
New York State Experience (2018-2021)
Nearly 650,000 infants were screened in the first 3 years, with 34 screening positive 3.
94% of identified infants received treatment, with the overwhelming majority (94%; 30/32) receiving gene replacement therapy 3.
Most infants were treated before 6 weeks of age (median = 34.5 days of life; range 11-180 days) 3.
All infants with 3 copies of SMN2 remained clinically asymptomatic post-treatment, while those with 2 copies showed more variable outcomes 3.
California Experience (2020-2021)
628,791 newborns were tested in the first 18 months, with 34 screening positive 6.
Infants were referred, diagnosed, and treated at a median of 8,12, and 33 days of life, respectively 6.
62% received treatment while still asymptomatic, demonstrating the screening program's effectiveness in enabling early intervention 6.
Common Barriers to Timely Treatment
Medical Delays
Presence of AAV9 antibodies (relevant for gene replacement therapy) 3.
Elevated troponin I levels requiring medical clearance 3.
Non-Medical Barriers
Delays in obtaining insurance authorization 3.
Insurance policies restricting coverage for specific treatment modalities 3.
Important Caveats
The variability in age at symptom onset means some asymptomatic patients identified through screening may not require therapy for years or decades, raising ethical considerations about early identification 4.
A long-term follow-up registry is ethically essential to ensure benefits outweigh harms for all screened infants, including those with milder and/or later-onset forms of SMA 4.
The incidence observed in screened populations remains lower than previously predicted, affecting resource allocation and counseling approaches 3.