In terms of therapy, whereas valproate is contraindicated in other mitochondrial encephalopathies, such as Alpers syndrome due to pathogenic variants in POLG (DNA polymerase γ), as it can lead to fulminant liver failure (Pronicka et al., 2011), there are no definite data on valproate toxicity in PARS2‐related DEE. This evidence concerns the gene POLG and Mitochondrial encephalopathy.