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

Abstract

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...

Intragenic and structural variation in the SMN locus and clinical variability in spinal muscular atrophy

“…Although inter-sample variation of the MLPA in our repeated analysis was very low (3%), for eight out of 286 patients (3%), it was not possible to determine whether they had three or four copies. This may raise difficulties in some countries, where there is no reimbursement of antisense-oligonucleotide (ASO) therapy for patients with more than three SMN2 copies, or in prenatal screening programmes where a similar cut-off might be used ( Baker et al , 2019 ; Muller-Felber et al , 2020 ). Intronic sequence variation is a possible explanation for differences in treatment response.…”

Longitudinal Evaluation of Working Memory in Duchenne Muscular Dystrophy

“…The average life expectancy in DMD now extends to the third-to-fourth decade of life [65,66], and corticosteroids and standard-of-care guidelines addressing the many facets of the disease have improved clinical outcomes in DMD. Adeno-associated-virus-based gene therapy to restore skeletal and cardiac health is currently in phase 2 clinical trial; this new treatment frontier combined with approval of newborn screening for DMD by the Food and Drug Administration Agency offers the opportunity to strategize treatment options for those showing cognitive deficits while planning for ways to prevent developmental problems before they arise [67]. The research intensity in DMD continues to be focused overwhelmingly on skeletal and cardiac health.…”

Is Newborn Screening the Ultimate Strategy to Reduce Diagnostic Delays in Pompe Disease? The Parent and Patient Perspective

“…Population NBS for PD was first implemented in Taiwan in 2005. A decade later, in 2015, it was added to the USA Department of Health and Human Services-endorsed Recommended Uniform Screening Panel (RUSP) [19]. As of November 2019, implementation has occurred in 23 states and a further 9 states are actively pursuing implementation or conducted pilot studies [20].…”

“…Pilot NBS studies have also been conducted in Austria, Italy, Hungary, and Japan [21]. Whilst establishment of these programs is challenging and controversial, key driving factors include [19]:…”

“…Pilot NBS studies have also been conducted in Austria, Italy, Hungary, and Japan [ 21 ]. Whilst establishment of these programs is challenging and controversial, key driving factors include [ 19 ]: The development of promising new treatment options; Advances in screening technology; Advocacy by special interest groups. …”