A Voluntary Statewide Newborn Screening Pilot for Spinal Muscular Atrophy: Results from Early Check

Abstract

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS.

The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health

“…A more recent example of NBS utilizing DNA extracted from DBS as a primary target is SMN1 -related spinal muscular atrophy (SMA), which was added to the RUSP in 2018 ( 31 , 37 ). SMN1 -related SMA is a progressive disorder characterized by muscle weakness due to loss of anterior horn cells and has a broad phenotypic spectrum ranging from a severe neonatal presentation with weakness, hypotonia, respiratory failure, and death in early infancy to an adult-onset presentation of muscle weakness without respiratory insufficiency and with a normal lifespan ( 31 ).…”

“…Treatment for SMN1 -related SMA has recently become available and slows or prevents the progression of the disorder once therapy is initiated, thus making it an ideal candidate for NBS ( 31 ). Screening identifies a common gene deletion, and as for SCID, the primary screen is a quantitative PCR technique; combining SCID and SMA in one newborn screen assay has been proposed ( 37 ). For both of these conditions, DNA is used for the primary screen but neither employs DNA sequencing.…”

Newborn screening of neuromuscular diseases

“…NBS for SMA has been reported in nine countries / subnational regions [18][19][20][21][22][23][24][25] . The first pilots were implemented in 2014 in Taiwan [18] , and in New-York in 2016 [19] .…”

Detection of Spinal Muscular Atrophy Patients Using Dried Saliva Spots

“…These drugs give better outcomes when treatment is initiated at an early stage, before the onset of symptoms [12][13][14]. Therefore, there is a growing implementation of newborn screening programs for SMA (NBS-SMA) worldwide [7,[15][16][17][18][19][20][21]. Technically, the current NBS-SMA program can detect all SMA patients with a homozygous deletion regardless of the clinical subtype.…”