Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

Hale, Jaime E.; Darras, Basil T.; Swoboda, Kathryn J.; Estrella, Elicia; Chen, Jin Yun Helen; Abbott, Mary‐Alice; Hay, Beverly N.; Kumar, Binod; Counihan, Anne M.; Gerstel-Thompson, Jacalyn L.; Sahai, Inderneel; Eaton, Roger B.; Comeau, Anne Marie

doi:10.3390/ijns7020026

Cited by 17 publications

(13 citation statements)

References 11 publications

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“…Some programs implement a digital drop PCR or a reverse-transcriptase (RT) PCR second-tier methodology to determine the SMN2 copy number as well ( n = 8), while other programs repeat the first-tier methodology on the original dried blood spot on the next day (a confirmation duplicate). Five states offer a three-tier, high-throughput screening algorithm [ 11 ]. Not all programs implement a second-tier screen, reflexing the newborn screening risk assessment results to a clinical laboratory.…”

Section: Sma Screening Methodsmentioning

confidence: 99%

“…^ While many states do not have a second-tier screen for SMA, many will perform a confirmation duplicate by using the same dried blood spot to repeat the qPCR for SMN1 exon 7 deletion the following day. ** Massachusetts has developed, validated and implemented a three-tier, high-throughput algorithm for the detection of SMA-detected infants in Massachusetts, Maine, New Hampshire, Rhode Island, and Vermont [ 11 ].…”

Section: Table A1mentioning

confidence: 99%

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Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021

Hale

Ojodu

Singh

2021

IJNS

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Newborn screening (NBS) programs identify newborns at increased risk for genetic disorders, linking these newborns to timely intervention and potentially life-saving treatment. In the United States, the Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) recommends the disorders for state NBS programs to screen. ACHDNC updated the Recommended Uniform Screening Panel to include Spinal Muscular Atrophy (SMA) in July 2018. As of June 2021, 34 state NBS programs had fully implemented SMA newborn screening, and at least 8 programs were pursuing implementation. This article will review current SMA screening processes, considerations, challenges, and status.

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Section: Sma Screening Methodsmentioning

confidence: 99%

Section: Table A1mentioning

confidence: 99%

Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021

Hale

Ojodu

Singh

2021

IJNS

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“…During the clinical encounter, treatment options are reviewed with the caregivers and if needed, additional laboratory testing is performed to determine which treatment is indicated. Although there are significant practice variations across the United States, in general, the sense of urgency and need for early evaluation is universal ( 14 ).…”

Section: From Diagnosis To the Delivery Of Therapiesmentioning

confidence: 99%

Addressing the implementation gap in advanced therapeutics for spinal muscular atrophy in the era of newborn screening programs

2022

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Spinal muscular atrophy (SMA) is a rare genetic disease that results in progressive neuromuscular weakness. Without therapy, the most common form of the disease, type 1, typically results in death or chronic respiratory failure in the first 2 years of life. Thanks to the recent introduction of newborn screening programs and the discovery of three disease-modifying therapies in the last decade, the outcomes of children with SMA have dramatically improved. Patients are able to achieve many, if not all, of the typical neuromotor milestones, such as sitting, standing and walking, as well as safe oral intake. As the natural history of treated patients is continuously evolving, children with SMA continue to require complex and multidisciplinary care, posing implementation and sustainability challenges. Accordingly, there is a significant need for the application and evaluation of implementation science to address the steps involved in the diagnosis and treatment of patients with SMA, ensuring that all pertinent stakeholders and systems are working effectively to deliver timely and appropriate care. In this manuscript, we discuss the current challenges and gaps in the care for children with SMA, as well as how implementation science can advance this field. In addition, we provide an adapted implementation science framework that includes the main domains and subdomains involved in the care of patients with SMA.

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“…Specifically, as attractive as the "locked nucleic acid" approach seemed to be for enhancing specificity of primer and probe binding, there was no experience within the high-throughput environment of newborn screening programs at the time and we opted for a more conservative approach. Our screening algorithm uses modifications of two independent CDC-developed RealTime™ PCR-based assays [11][12][13]and applies them in two assays (Assay A and Assay B) across two tiers [14]. The first tier comprises only Assay A, which is highly sensitive for the detection of absent SMN1 Exon 7.…”

Section: Introductionmentioning

confidence: 99%

Novel Modification of a Confirmatory SMA Sequencing Assay that Can Be Used to Determine SMN2 Copy Number

Kumar

Barton

Kordowska

et al. 2021

IJNS

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Promising treatments for spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, prompted calls for inclusion in newborn screening (NBS). In January 2018, the New England Newborn Screening Program (NENSP) began statewide screening for SMA using a tiered algorithm looking for the absence of SMN1 Exon 7. When results from the first and second tier needed reconciliation, we developed and validated a third tier DNA sequencing assay to ensure the presence or absence of SMN1 Exon 7. All nine infants referred to specialty centers through NBS showed single base substitution of c.840C>T, and were confirmed to have SMA. Further, a minor sequencing protocol modification allowed the estimation of SMN2 copy number in SMA affected patients; we developed and validated a copy-number assay yielding 100% match with seven previously characterized specimens of SMA patients. All nine SMA-affected infants found through NBS were also assayed for SMN2 copy number. Results were comparable but not 100% matched with those that were reported by independent diagnostic laboratories. In conclusion, a sequencing protocol confirms NBS findings from real-time qPCR, and its modified application allows NBS programs that have sequencing capabilities to provide SMN2 copy numbers without the need for additional instrumentation.

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Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

Cited by 17 publications

References 11 publications

Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021

Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021

Addressing the implementation gap in advanced therapeutics for spinal muscular atrophy in the era of newborn screening programs

Novel Modification of a Confirmatory SMA Sequencing Assay that Can Be Used to Determine SMN2 Copy Number

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