Correspondence on: “Discrepancy in Spinal Muscular Atrophy Incidence findings in newborn screening programs: the influence of carrier screening?” by Kay et al

2020 ◽  
Vol 22 (11) ◽  
pp. 1913-1914
Author(s):  
Tamara Dangouloff ◽  
François Boemer ◽  
Jean-Hubert Caberg ◽  
Laurent Servais
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Muscular Atrophy ◽  
Carrier Screening ◽  
Screening Programs

scholarly journals Validation of a Fast, Robust, Inexpensive, Two-Tiered Neonatal Screening Test algorithm on Dried Blood Spots for Spinal Muscular Atrophy

2019 ◽  
Vol 5 (2) ◽  
pp. 21 ◽  
Author(s):  
Annuska Strunk ◽  
Andre Abbes ◽  
Antoine Stuitje ◽  
Chris Hettinga ◽  
Eline Sepers ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Neonatal Screening ◽  
Muscular Atrophy ◽  
Melting Curve ◽  
Curve Analysis ◽  
Melting Curve Analysis ◽  
Smn1 Gene ◽  
Screening Programs ◽  
Crude Extracts

Spinal muscular atrophy (SMA) is one of the leading genetic causes of infant mortality with an incidence of 1:10,000. The recently-introduced antisense oligonucleotide treatment improves the outcome of this disease, in particular when applied at an early stage of progression. The genetic cause of SMA is, in >95% of cases, a homozygous deletion of the survival motor neuron 1 (SMN1) gene, which makes the low-cost detection of SMA cases as part of newborn screening programs feasible. We developed and validated a new SALSA MC002 melting curve assay that detects the absence of the SMN1 exon 7 DNA sequence without detecting asymptomatic carriers and reliably discriminates SMN1 from its genetic homolog SMN2 using crude extracts from newborn screening cards. Melting curve analysis shows peaks specific for both the SMN1 gene and the disease modifying SMN2 homolog. The detection of the SMN2 homolog, of which the only clinically relevant difference from the SMN1 gene is a single nucleotide in exon 7, was only used to confirm a correct reaction in samples that lacked the SMN1 gene, and not for SMN2 quantification. We retrieved 47 DBS samples from children with genetically-confirmed SMA, after informed consent from parents, and 375 controls from the national archive of the Dutch National Institute for Public Health and the Environment (RIVM). The assay correctly identified all anonymized and randomized SMA and control samples (i.e., sensitivity and specificity of 100%), without the detection of carriers, on the three most commonly-used PCR platforms with melting curve analysis. This test’s concordance with the second-tier ‘golden standard’ P021 SMA MLPA test was 100%. Using the new P021–B1 version, crude extracts from DBS cards could also be used to determine the SMN2 copy number of SMA patients with a high level of accuracy. The MC002 test showed the feasibility and accuracy of SMA screening in a neonatal screening program.

scholarly journals Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
François Boemer ◽  
Jean-Hubert Caberg ◽  
Pablo Beckers ◽  
Vinciane Dideberg ◽  
Samantha di Fiore ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Screening Program ◽  
Muscular Atrophy ◽  
The United States ◽  
Lessons Learned ◽  
European Medicines Agency ◽  
Pilot Program ◽  
Screening Programs ◽  
New Therapies

AbstractThree new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.

scholarly journals Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

2021 ◽  
Vol 7 (2) ◽  
pp. 26
Author(s):  
Jaime E. Hale ◽  
Basil T. Darras ◽  
Kathryn J. Swoboda ◽  
Elicia Estrella ◽  
Jin Yun Helen Chen ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
New England ◽  
Screening Program ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Newborn Screening Program ◽  
Treatment Protocols ◽  
Screening Algorithm ◽  
New Treatment

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit.

Newborn screening for spinal muscular atrophy: Anticipating an imminent need

2015 ◽  
Vol 39 (3) ◽  
pp. 217-229 ◽  
Author(s):  
Han C. Phan ◽  
Jennifer L. Taylor ◽  
Harry Hannon ◽  
Rodney Howell
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Muscular Atrophy

Integrating a Pilot Newborn Screening for Spinal Muscular Atrophy Into the Australian Public Healthcare System

2021 ◽  
Author(s):  
Arlene M. D'Silva ◽  
Hugo Sampaio ◽  
Didu Sanduni Thamarasa Kariyawasam ◽  
David Mowat ◽  
Jacqui Russell ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Healthcare System ◽  
Muscular Atrophy ◽  
Public Healthcare ◽  
Public Healthcare System

Newborn screening for spinal muscular atrophy with disease-modifying therapies: a cost-effectiveness analysis

2021 ◽  
pp. jnnp-2021-326344
Author(s):  
Sophy TF Shih ◽  
Michelle Anne Farrar ◽  
Veronica Wiley ◽  
Georgina Chambers
Keyword(s):  
Gene Therapy ◽  
Cost Effectiveness ◽  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Markov Models ◽  
Muscular Atrophy ◽  
Early Gene ◽  
Sensitivity Analyses ◽  
Life Years ◽  
Late Treatment

ObjectiveTo assess cost-effectiveness of newborn screening (NBS) for spinal muscular atrophy (SMA) and early treatment with nusinersen or onasemnogene abeparvovec (gene therapy), compared with nusinersen without SMA screening.MethodsInformed by an Australian state-wide SMA NBS programme, a decision analytical model nested with Markov models was constructed to evaluate costs and quality-adjusted life-years (QALYs) from a societal perspective with sensitivity analyses.ResultsBy treating one presymptomatic SMA infant with nusinersen or gene therapy, an additional 9.93 QALYs were gained over 60 years compared with late treatment in clinically diagnosed SMA. The societal cost was $9.8 million for early nusinersen treatment, $4.4 million for early gene therapy and $4.8 million for late nusinersen treatment. Compared with late nusinersen treatment, early gene therapy would be dominant, gaining 9.93 QALYs while saving $360 000; whereas early nusinersen treatment would result in a discounted incremental cost-effectiveness ratio (ICER) of $507 000/QALY.At a population level, compared with no screening and late treatment with nusinersen, NBS and early gene therapy resulted in 0.00085 QALY gained over 60 years and saving $24 per infant screened (85 QALYs gained and $2.4 million saving per 100 000 infants screened). More than three quarters of simulated ICERs by probability sensitivity analyses showed NBS and gene therapy would be dominant or less than $50 000/QALY, compared with no screening and late nusinersen treatment.ConclusionNBS coupled with gene therapy improves the quality and length of life for infants with SMA and would be considered value-for-money from an Australian clinical and policy context.

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