Traumatic brain injury is unlikely precipitating Leigh syndrome due to the GJB2 mutation c.35delG

Dear Editor: With interest we read the article by Ashrafi et al. about a 14-year-old female who is regarded to have developed Leigh syndrome (LS) after traumatic brain injury (TBI) (1). We have the following comments and concerns: We do not agree with the notion that traumatic brain injury was the precipitating factor for LS. The patient had a history of hypoacusis, which is a typical clinical manifestation of a mitochondrial disorder (MID). Hypoacusis obviously had developed long before the TBI. Additionally, the patient was diagnosed with neuropathy of the peripheral nerves two months after TBI. It is rather unlikely that neuropathy was triggered by TBI and more likely it was already present before the trauma. Thus, the initial manifestations of LS in the presented patient were most likely hypoacusis followed by neuropathy and TBI only might have triggered the seizure but not the MID. Why was the patient put on phenytoin, which is well-known to be mitochondrion-toxic (2)? Phenytoin may worsen epilepsy and MID in general and it is conceivable that in fact phenytoin was responsible for worsening of the phenotype and not the TBI. In a 16-year-old female with MELAS syndrome due to the mutation m.3243A>G, phenytoin caused intestinal pseudo-obstruction one month after intravenous phenytoin for status epilepticus (3). In a patient with Kearns-Sayre syndrome phenytoin decreased cerebrospinal fluid (CSF) folate levels (4). In rat hepatocytes, phenytoin increased reactive oxygen species (ROS) formation, decreased intracellular reduced glutathione, increased intracellular oxidised glutathione, and enhanced lipid peroxidation and mitochondrial damage (5). In a hepatic microsomal system, phenytoin decreased state-3 respiration,