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


OBJECTIVE
To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Glascock|Jacqueline|J|', 'Sampson|Jacinda|J|', 'Haidet-Phillips|Amanda|A|', 'Connolly|Anne|A|', 'Darras|Basil|B|', 'Day|John|J|', 'Finkel|Richard|R|', 'Howell|R Rodney|RR|', 'Klinger|Katherine|K|', 'Kuntz|Nancy|N|', 'Prior|Thomas|T|', 'Shieh|Perry B|PB|', 'Crawford|Thomas O|TO|', 'Kerr|Douglas|D|', 'Jarecki|Jill|J|']
D000359:Aftercare D000465:Algorithms D002657:Child Development D056915:DNA Copy Number Variations D003697:Delphi Technique D019468:Disease Management D061345:Early Medical Intervention D004576:Electromyography D018628:Gene Dosage D006801:Humans D007223:Infant D007231:Infant, Newborn D009048:Motor Skills D015997:Neonatal Screening D009841:Oligonucleotides D016376:Oligonucleotides, Antisense D017410:Practice Guidelines as Topic D012720:Severity of Illness Index D014897:Spinal Muscular Atrophies of Childhood D055533:Survival of Motor Neuron 1 Protein D055540:Survival of Motor Neuron 2 Protein D013995:Time
algorithm spinal muscular atrophy Newborn screening SMN1 drug treatment survival motor neuron (SMN)