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

• Published in: Journal of neuromuscular diseases Vol. 5; no. 2; p. 145
• Main Authors: Glascock, Jacqueline, Sampson, Jacinda, Haidet-Phillips, Amanda, Connolly, Anne, Darras, Basil, Day, John, Finkel, Richard, Howell, R Rodney, Klinger, Katherine, Kuntz, Nancy, Prior, Thomas, Shieh, Perry B, Crawford, Thomas O, Kerr, Douglas, Jarecki, Jill
• Format: Journal Article
• Language: English
• Published: Netherlands 2018
• Subjects: Aftercare; Algorithms; Child Development; Delphi Technique; Disease Management; DNA Copy Number Variations; Early Medical Intervention; Electromyography; Gene Dosage; Humans; Infant; Infant, Newborn; Motor Skills; Neonatal Screening; Oligonucleotides - therapeutic use; Oligonucleotides, Antisense - therapeutic use; Practice Guidelines as Topic; Severity of Illness Index; Spinal Muscular Atrophies of Childhood - diagnosis; Spinal Muscular Atrophies of Childhood - drug therapy; Spinal Muscular Atrophies of Childhood - genetics; Spinal Muscular Atrophies of Childhood - physiopathology; Survival of Motor Neuron 1 Protein - genetics; Survival of Motor Neuron 2 Protein - genetics; Time; Newborn screening; survival motor neuron (SMN); spinal muscular atrophy; SMN1; algorithm; drug treatment
• ISSN: 2214-3599; 2214-3602
• DOI: 10.3233/JND-180304

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process.