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

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

doi:10.3233/JND-180304

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

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	145-158
Number of pages	14
Journal	Journal of neuromuscular diseases
Volume	5
Issue number	2
DOIs	https://doi.org/10.3233/JND-180304
State	Published - Jan 1 2018

Keywords

Newborn screening
SMN1
algorithm
drug treatment
spinal muscular atrophy
survival motor neuron (SMN)

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.3233/JND-180304

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Glascock, J., Sampson, J., Haidet-Phillips, A., Connolly, A., Darras, B., Day, J., Finkel, R., Howell, R. R., Klinger, K., Kuntz, N. L., Prior, T., Shieh, P. B., Crawford, T. O., Kerr, D., & Jarecki, J. (2018). Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening. Journal of neuromuscular diseases, 5(2), 145-158. https://doi.org/10.3233/JND-180304

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title = "Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening",

abstract = "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.",

keywords = "Newborn screening, SMN1, algorithm, drug treatment, spinal muscular atrophy, survival motor neuron (SMN)",

author = "Jacqueline Glascock and Jacinda Sampson and Amanda Haidet-Phillips and Anne Connolly and Basil Darras and John Day and Richard Finkel and Howell, {R. Rodney} and Katherine Klinger and Kuntz, {Nancy L} and Thomas Prior and Shieh, {Perry B.} and Crawford, {Thomas O.} and Douglas Kerr and Jill Jarecki",

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Glascock, J, Sampson, J, Haidet-Phillips, A, Connolly, A, Darras, B, Day, J, Finkel, R, Howell, RR, Klinger, K, Kuntz, NL, Prior, T, Shieh, PB, Crawford, TO, Kerr, D & Jarecki, J 2018, 'Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening', Journal of neuromuscular diseases, vol. 5, no. 2, pp. 145-158. https://doi.org/10.3233/JND-180304

TY - JOUR

T1 - Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening

AU - Glascock, Jacqueline

AU - Sampson, Jacinda

AU - Haidet-Phillips, Amanda

AU - Connolly, Anne

AU - Darras, Basil

AU - Day, John

AU - Finkel, Richard

AU - Howell, R. Rodney

AU - Klinger, Katherine

AU - Kuntz, Nancy L

AU - Prior, Thomas

AU - Shieh, Perry B.

AU - Crawford, Thomas O.

AU - Kerr, Douglas

AU - Jarecki, Jill

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Newborn screening

KW - SMN1

KW - algorithm

KW - drug treatment

KW - spinal muscular atrophy

KW - survival motor neuron (SMN)

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U2 - 10.3233/JND-180304

DO - 10.3233/JND-180304

M3 - Article

C2 - 29614695

AN - SCOPUS:85052819718

SN - 2214-3599

VL - 5

SP - 145

EP - 158

JO - Journal of neuromuscular diseases

JF - Journal of neuromuscular diseases

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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