Georgia state spinal muscular atrophy newborn screening experience: Screening assay performance and early clinical outcomes

Abstract

The purpose of this study is to provide the results of the newborn screening (NBS) program for Spinal Muscular Atrophy (SMA) in the state of Georgia to determine disease incidence, time to diagnosis and treatment, and early outcomes. NBS for SMA was performed using real time PCR assays from February 2019 through February 2020 in a pilot phase of screening. This method continued as part of our official state panel, and here we describe the pilot period as well as the first year of standard screening through February 2021. Medical records of infants with a positive NBS were reviewed for time to confirmation and neurologic evaluation, SMN2 copy number, clinical information, and treatment. Descriptive statistics were applied. Of the 301,418 samples screened, there were 15 true positive (eight males) and 24 false positive cases. One patient was missed due to human error early in the pilot phase and presented after symptom onset. The incidence of SMA in Georgia is approximately 1 in 18,840 births per year. After the pilot phase, the false positive rate was found to be so low that all patients who test positive were immediately referred to neurology for further care. Four patients died prior to intervention. Ten patients received intervention. Gene therapy was the preferred treatment. One patient was lost to follow-up; another was clinically followed. In conclusion, trends for treated patients show improved or stable motor function. Long-term follow-up will help determine the durability of treatment.

Newbornscreening SMA – From Pilot Project to Nationwide Screening in Germany

“…Given the enormous psychological impact of a false positive result on the family, care must be taken to ensure that the number of false positives approaches zero [12,19]. Figures such as 61% of suspicious results which could not be confirmed in a pilot project are definitely too high [20]. To improve the quality of NBS, both preanalytical and analytical problems need to be addressed.…”

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…Real-world studies conducted in various countries, particularly those linked to expanded newborn screening (NBS) programs, have consistently shown that early initiation of gene replacement therapy in pre-symptomatic infants with SMA-5q results in remarkable developmental progress, with children achieving motor milestones within the expected developmental timeframe. 108 113 114 115 Furthermore, cost-effectiveness studies, particularly in countries like Australia, have shown that implementing neonatal screening for SMA-5q, coupled with early gene replacement therapy treatment, leads to reduced costs or remains within the cost-effectiveness threshold considered by these countries in the long term. 116 …”

Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health

“…One of the reasons for the minimal effect of VE alone on the pro-inflammatory effect may be related to less toxic chemicals contained in VE as compared to tobacco (regular) cigarettes. [42][43][44] There are several limitations to our study. First, we only included one human donor in this pilot study, requiring validation in future experiments.…”

“…One of the reasons for the minimal effect of VE alone on the pro-inflammatory effect may be related to less toxic chemicals contained in VE as compared to tobacco (regular) cigarettes. 42 – 44 …”