Cargando…

Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9

An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9-dependent metabolism seem to play some role in the age-related di...

Descripción completa

Detalles Bibliográficos
Autores principales: Nagy, Andrea, Bűdi, Tamás, Temesvári, Manna, Szever, Zsuzsa, Szabó, Pál Tamás, Monostory, Katalin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588450/
https://www.ncbi.nlm.nih.gov/pubmed/26543813
http://dx.doi.org/10.1016/j.ebcr.2015.08.006
_version_ 1782392628767096832
author Nagy, Andrea
Bűdi, Tamás
Temesvári, Manna
Szever, Zsuzsa
Szabó, Pál Tamás
Monostory, Katalin
author_facet Nagy, Andrea
Bűdi, Tamás
Temesvári, Manna
Szever, Zsuzsa
Szabó, Pál Tamás
Monostory, Katalin
author_sort Nagy, Andrea
collection PubMed
description An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9-dependent metabolism seem to play some role in the age-related differences in the incidence of adverse events. We present the case of a premature patient with moderate hemorrhage in the subependymal region (grade II — intraventricular hemorrhage without ventricular dilatation), several myoclonic episodes in her right upper arm (series of jerks lasting milliseconds), and epileptiform abnormalities on the EEG (localized spike-and-wave in the left frontal region with preserved background activity who was treated with valproate. Serious side effects, consisting of bone marrow depression, hyperammonemia, and serum alkaline phosphatase elevation, were observed seventeen days after the beginning of valproate therapy. The toxic symptoms were likely the consequence of a reduced ability to metabolize valproate. The patient was demonstrated to carry two loss-of-function mutations in CYP2C9 (CYP2C9*3/*3) resulting in exaggerated blood concentrations of valproate. The present case highlights the importance of assaying inborn errors in CYP2C9 gene in pediatric patients to avoid valproate-evoked serious side effects.
format Online
Article
Text
id pubmed-4588450
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-45884502015-11-05 Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9 Nagy, Andrea Bűdi, Tamás Temesvári, Manna Szever, Zsuzsa Szabó, Pál Tamás Monostory, Katalin Epilepsy Behav Case Rep Case Report An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9-dependent metabolism seem to play some role in the age-related differences in the incidence of adverse events. We present the case of a premature patient with moderate hemorrhage in the subependymal region (grade II — intraventricular hemorrhage without ventricular dilatation), several myoclonic episodes in her right upper arm (series of jerks lasting milliseconds), and epileptiform abnormalities on the EEG (localized spike-and-wave in the left frontal region with preserved background activity who was treated with valproate. Serious side effects, consisting of bone marrow depression, hyperammonemia, and serum alkaline phosphatase elevation, were observed seventeen days after the beginning of valproate therapy. The toxic symptoms were likely the consequence of a reduced ability to metabolize valproate. The patient was demonstrated to carry two loss-of-function mutations in CYP2C9 (CYP2C9*3/*3) resulting in exaggerated blood concentrations of valproate. The present case highlights the importance of assaying inborn errors in CYP2C9 gene in pediatric patients to avoid valproate-evoked serious side effects. Elsevier 2015-09-22 /pmc/articles/PMC4588450/ /pubmed/26543813 http://dx.doi.org/10.1016/j.ebcr.2015.08.006 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Case Report
Nagy, Andrea
Bűdi, Tamás
Temesvári, Manna
Szever, Zsuzsa
Szabó, Pál Tamás
Monostory, Katalin
Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title_full Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title_fullStr Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title_full_unstemmed Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title_short Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9
title_sort adverse events in a newborn on valproate therapy due to loss-of-function mutations in cyp2c9
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588450/
https://www.ncbi.nlm.nih.gov/pubmed/26543813
http://dx.doi.org/10.1016/j.ebcr.2015.08.006
work_keys_str_mv AT nagyandrea adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9
AT buditamas adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9
AT temesvarimanna adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9
AT szeverzsuzsa adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9
AT szabopaltamas adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9
AT monostorykatalin adverseeventsinanewbornonvalproatetherapyduetolossoffunctionmutationsincyp2c9