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- AAV:
- adeno-associated virus
- AAV9:
- adeno-associated virus serotype 9
- ACHDNC:
- Advisory Committee on Heritable Disorders in Newborns and Children
- ACMG:
- American College of Medical Genetics and Genomics
- CHERISH:
- A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants with Later-onset Spinal Muscular Atrophy
- ENDEAR:
- Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
- FDA:
- Food and Drug Administration
- G-tube:
- gastrostomy tube
- HRSA:
- Health Resources and Services Administration
- ISS-N1:
- intronic splicing silencer N1
- NBS:
- newborn screening
- PCR:
- polymerase chain reaction
- RT-PCR:
- real-time polymerase chain reaction
- RUSP:
- recommended uniform screening panel
- SCID:
- severe combined immunodeficiency
- SHINE:
- A Study for Participants with Spinal Muscular Atrophy Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
- SMA:
- spinal muscular atrophy
- SMN:
- survival motor neuron
- TREC:
- T-cell receptor excision circle
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletions or mutations in the survival motor neuron (SMN1) gene. SMA is characterized by loss of lower motor neurons (anterior horn cells) in the spinal cord and brainstem nuclei, leading to progressive symmetrical muscle weakness and atrophy. It affects approximately 1 in 6,000 to 1 in 10,000 individuals and is the most common inherited cause of childhood mortality, but this may soon change given recent developments. In December 2016, nusinersen, an antisense oligonucleotide drug, was approved by the United States Food and Drug Administration for the treatment of SMA, and in July 2018, SMA was added to the recommended uniform screening panel, a list of conditions that all states are encouraged to include in their newborn screening (NBS) panels. In this review, we begin with a brief clinical history of the diagnosis of SMA, discuss the current SMA clinical classification system, describe the current treatment, and discuss evolving treatment guidelines. We then discuss the path to include SMA in NBS programs as well as the controversies it engenders because the variability in age at symptom onset means early identification of asymptomatic patients who will not require therapy for years or decades. We also consider alternate population screening opportunities. Next, we consider experimental treatments. We conclude by supporting NBS for SMA with the caveat that a long-term follow-up registry is ethically essential to ensure that the benefits outweigh the harms for all screened infants, including those with milder and/or later-onset forms of SMA.
- Copyright © 2019 by the American Academy of Pediatrics
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