Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia

Kendra J. Bjoraker; Michael A. Swanson; Curtis R. Coughlin; John Christodoulou; Ee S. Tan; Mark Fergeson; Sarah Dyack; Ayesha Ahmad; Marisa W. Friederich; Elaine B. Spector; Geralyn Creadon-Swindell; M. Antoinette Hodge; Sommer Gaughan; Casey Burns; Johan L K Van Hove

doi:10.1016/j.jpeds.2015.12.027

Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia

Kendra J. Bjoraker, Michael A. Swanson, Curtis R. Coughlin, John Christodoulou, Ee S. Tan, Mark Fergeson, Sarah Dyack, Ayesha Ahmad, Marisa W. Friederich, Elaine B. Spector, Geralyn Creadon-Swindell, M. Antoinette Hodge, Sommer Gaughan, Casey Burns, Johan L K Van Hove^*

^*Corresponding author for this work

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

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Abstract

Objective To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia.

Study design: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures.

Results: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication.

Conclusions: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

Original language	English
Pages (from-to)	234-239
Number of pages	6
Journal	Journal of Pediatrics
Volume	170
DOIs	https://doi.org/10.1016/j.jpeds.2015.12.027
Publication status	Published - 1 Mar 2016
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Bjoraker, K. J., Swanson, M. A., Coughlin, C. R., Christodoulou, J., Tan, E. S., Fergeson, M., Dyack, S., Ahmad, A., Friederich, M. W., Spector, E. B., Creadon-Swindell, G., Hodge, M. A., Gaughan, S., Burns, C., & Van Hove, J. L. K. (2016). Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia. Journal of Pediatrics, 170, 234-239. https://doi.org/10.1016/j.jpeds.2015.12.027

@article{2dea20ea56594303aaa1a981e197b333,

title = "Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia",

abstract = "Objective To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. Study design: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. Results: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. Conclusions: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.",

author = "Bjoraker, {Kendra J.} and Swanson, {Michael A.} and Coughlin, {Curtis R.} and John Christodoulou and Tan, {Ee S.} and Mark Fergeson and Sarah Dyack and Ayesha Ahmad and Friederich, {Marisa W.} and Spector, {Elaine B.} and Geralyn Creadon-Swindell and Hodge, {M. Antoinette} and Sommer Gaughan and Casey Burns and {Van Hove}, {Johan L K}",

note = "Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2016",

month = mar,

day = "1",

doi = "10.1016/j.jpeds.2015.12.027",

language = "English",

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Bjoraker, KJ, Swanson, MA, Coughlin, CR, Christodoulou, J, Tan, ES, Fergeson, M, Dyack, S, Ahmad, A, Friederich, MW, Spector, EB, Creadon-Swindell, G, Hodge, MA, Gaughan, S, Burns, C & Van Hove, JLK 2016, 'Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia', Journal of Pediatrics, vol. 170, pp. 234-239. https://doi.org/10.1016/j.jpeds.2015.12.027

TY - JOUR

T1 - Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia

AU - Bjoraker, Kendra J.

AU - Swanson, Michael A.

AU - Coughlin, Curtis R.

AU - Christodoulou, John

AU - Tan, Ee S.

AU - Fergeson, Mark

AU - Dyack, Sarah

AU - Ahmad, Ayesha

AU - Friederich, Marisa W.

AU - Spector, Elaine B.

AU - Creadon-Swindell, Geralyn

AU - Hodge, M. Antoinette

AU - Gaughan, Sommer

AU - Burns, Casey

AU - Van Hove, Johan L K

N1 - Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Objective To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. Study design: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. Results: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. Conclusions: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

AB - Objective To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. Study design: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. Results: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. Conclusions: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

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U2 - 10.1016/j.jpeds.2015.12.027

DO - 10.1016/j.jpeds.2015.12.027

M3 - Article

C2 - 26749113

AN - SCOPUS:84960465993

SN - 0022-3476

VL - 170

SP - 234

EP - 239

JO - Journal of Pediatrics

JF - Journal of Pediatrics

ER -

Neurodevelopmental outcome and treatment efficacy of benzoate and dextromethorphan in siblings with attenuated nonketotic hyperglycinemia

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