Background: Mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) play a vital role in mitochondrial protein synthesis by attaching amino acids to the tRNA tails, have increasingly been associated with various neurological disorders. Methods: We reviewed the clinical characteristics and genetic findings of patients with epilepsy who were diagnosed with mt-aaRSs disorders. Results: From January 2016 to December 2022, 3,777 patients underwent exome sequencing. One hundred and thirty-three patients were diagnosed with epilepsy. Five patients from four families harbored pathogenic or likely pathogenic variants in genes encoding mt-aaRSs, including one case of AARS, three cases of FARS2, and one case of RARS2. All patients presented with drug-resistant epilepsy. The siblings with an FARS2 gene mutation represent the first reported cases of this gene causing childhood-onset progressive myoclonic epilepsy. Neuroimaging revealed brain atrophy in 4 patients. Two of our patients passed away during follow-up. The outcomes in the other three ranged from mild to severe global developmental delay. The clinical and laboratory data were variable. Genetic testing should be considered to establish the diagnosis of mt-aaRSs disorder. Conclusion: This study expands the phenotype of genetic defects in the mt-aaRSs genes, with an emphasis on the wide range of epilepsy onset.

Thitiporn Fangsaad
Bhumibol Adulyadej Hospital
Thailand

Chupong Ittiwut
Chulalongkorn University
Thailand

Vitchayaporn Emarach Saengow
Maharat Nakhon Ratchasima Hospital
Thailand

Kamornwan Katanyuwong
Maharaj Nakorn Chiang Mai
Thailand

Suda Jirasakuldej
Chulalongkorn University
Thailand

Ponghatai Boonsimma
Chulalongkorn University
Thailand

Tayard Desudchit
Chulalongkorn University
Thailand

Vorasuk Shotelersuk
Chulalongkorn University
Thailand

Sirorat Suwannachote
Queen Sirikit National Institute of Child Health
Thailand