Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening

Glascock, Jacqueline J.; Sampson, Jacinda B.; Haidet-Phillips, Amanda M.; Connolly, Anne M.; Darras, Basil T.; Day, John W.; Finkel, Richard S.; Howell, R. Rodney; Klinger, Katherine W.; Kuntz, Nancy L.; Prior, Thomas W.; Shieh, Perry B.; Crawford, Thomas O.; Kerr, Douglas A.; Jarecki, Jill

doi:10.3233/jnd-180304

Cited by 155 publications

(156 citation statements)

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“…Currently, the initial attempt to solve this dilemma was to find consensus on the opinion of experts assessed via the Delphi questionnaire [16]. Unfortunately, the expert group did not find a definite answer to the question of which children should be treated.…”

Section: Discussionmentioning

confidence: 99%

“…MLPA was repeated again in 2020 with an improved MPLA-test. The patients were advised according to the treatment algorithm published by the American SMA NBS Multidisciplinary Working Group [16].…”

Section: Methodsmentioning

confidence: 99%

“…Since a number of SMN-dependent and SMNindependent therapies are available [11], the timing of treatment is crucial for a good outcome [12,13] and available data show that presymptomatic treatment is superior to treatment after onset of symptoms [14] experts agree that newborn screening should be established [15,[16][17][18][19][20][21][22][23]. Currently first pilot projects for a genetic NBS in SMA are underway [18,[24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

“…Genetic data of SMA patients' relatives show that single cases exist [7] with a late onset of the disease although carrying a homozygous deletion of the SMN1-gene. Based on this finding, the American SMA NBS Multidisciplinary Working Group [16] recommended applying a strict follow-up strategy in these patients, well knowing that the overwhelming majority of patients with 4 and more SMN2 copies are expected to develop a loss of motoneurons which could be prevented by early treatment.…”

Section: Introductionmentioning

confidence: 99%

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Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

Müller‐Felber

Vill

Schwartz

et al. 2020

JND

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Although the value of newborn screening (NBS) for early detection and treatment opportunity in SMA patients is generally accepted, there is still an ongoing discussion about the best strategy in children with 4 and more copies of the SMN2 gene. This gene is known to be the most important but not the only disease modifier.In our SMA-NBS pilot project in Germany comprising 278,970 infants screened between January 2018 and November 2019 were 38 positive cases with a homozygous SMN1 deletion. 40% of them had 4 or more SMN2 copies. The incidence for homozygous SMN1 deletion was 1 : 7350, which is within the known range of SMA incidence in Germany.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

Müller‐Felber

Vill

Schwartz

et al. 2020

JND

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“…Additional NBS efforts for SMA are ongoing globally and are supported by the general population in several countries [17-19 , 38 , 39] . A treatment algorithm based on SMN2 copy number for SMA positive infants identified though NBS was recently developed by a group of SMA experts [40] . The recommendation was for infants with two or three SMN2 copies to receive immediate treatment following confirmatory testing.…”

Section: Discussionmentioning

confidence: 99%

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

Vivo

Bertini

Swoboda

et al. 2019

Neuromuscular Disorders

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421

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Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.

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Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening

et al. 2019

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ewborn screening (NBS) allows for earliest possible diagnosis and intervention for congenital diseases. For neuromuscular diseases (NMDs) such as Pompe disease, spinal muscular atrophy (SMA), and Duchenne muscular dystrophy (DMD), early diagnosis and initiation of treatment in the presymptomatic phase improves clinical outcomes. 1,2 Newborn screening was introduced in the early 1960s as a public health program in the United States and has expanded around the world. 3,4 The diseases screened and the screening processes vary from country to country. 3,4 In the United States, the list of screened diseases is made at the state level, based on the US Department of Health and Human Services-endorsed Recommended Uniform Screening Panel (RUSP). 5 However, diseases may be added to a state panel independent of RUSP approval. 6 Newborn screening programs in Europe are heterogenous, with no consensus on included conditions. 7,8 Many developing countries do not yet have organized NBS processes and have faced challenges in implementing NBS owing to economic and cultural barriers. 4 In this article, we will discuss challenges to implementing NBS for NMDs in the United States and how overcoming those challenges can maximize the potential of newly available life-saving therapies. DiscussionNewborn Screening: The US Experience Conditions to be included on the RUSP are recommended to the US Department of Health and Human Services by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC), 6,9 created by the US Congress to promote a uniform national NBS panel of diseases that meet evidence-based requirements (Box). 6,[9][10][11] The RUSP list includes 35 core and 26 secondary conditions. 6,10 During the review process, the committee considers the evidence of a reliable confirmatory diagnostic test, approved effective treatment, and how early intervention can reduce morbidity. Additionally, cost-effectiveness analysis and public health readiness are evaluated prior to addition of a condition to the RUSP but do not preclude the addition of a condition to the panel. 12 IMPORTANCE Newborn screening (NBS) identifies infants with specific congenital disorders for which earlier intervention cannot only prevent a lifetime of chronic disability but also, most importantly, save lives. In this article, we discuss complexities associated with NBS processes in the United States, with a focus on challenges in neuromuscular disorders.OBSERVATIONS As new interventions for neuromuscular disorders become available, the clinical community must prepare to overcome the challenges of adding new diseases to screening panels and understand the rigorous evidence review at the federal level and the complex process of state-level implementation. In this regard, NBS programs for Pompe disease and spinal muscular atrophy can guide the path of Duchenne muscular dystrophy and other neuromuscular disorders as future candidates for NBS. CONCLUSIONS AND RELEVANCEThe availability of advanced screening methods, the emergence of effective treatm...

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Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening

Cited by 155 publications

References 40 publications

Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening

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