Back to Search Start Over

Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis

Authors :
Patrick F Chinnery
Rita Horvath
Nour Elkhateeb
Katherine Schon
Thiloka E Ratnaike
Angela Lochmüller
Christopher Gilmartin
Source :
BMJ Neurology Open, Vol 6, Iss 1 (2024)
Publication Year :
2024
Publisher :
BMJ Publishing Group, 2024.

Abstract

Background We aimed to determine whether sodium valproate (VPA) should be contraindicated in all mitochondrial diseases, due to known VPA-induced severe hepatotoxicity in some mitochondrial diseases.Methods We systematically reviewed the published literature for mitochondrial DNA (mtDNA) and common nuclear genotypes of mitochondrial diseases using PubMed, Ovid Embase, Ovid Medline and MitoPhen databases. We extracted patient-level data from peer-reviewed articles, published until July 2022, using the Human Phenotype Ontology to manually code clinical presentations for 156 patients with genetic diagnoses from 90 publications.Results There were no fatal adverse drug reactions (ADRs) in the mtDNA disease group (35 patients), and only 1 out of 54 patients with a non-POLG mitochondrial disease developed acute liver failure. There were fatal outcomes in 53/102 (52%) POLG VPA-exposed patients who all harboured recessive mutations.Conclusions Our findings confirm the high risk of severe ADRs in any patient with recessive POLG variants irrespective of the phenotype, and therefore recommend that VPA is contraindicated in this group. However, there was limited evidence of toxicity to support a similar recommendation in other genotypes of mitochondrial diseases.

Details

Language :
English
ISSN :
26326140
Volume :
6
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMJ Neurology Open
Publication Type :
Academic Journal
Accession number :
edsdoj.fb5ec582cd4348f697749b386c6430fa
Document Type :
article
Full Text :
https://doi.org/10.1136/bmjno-2024-000650