Abstract
BACKGROUND: Aminoacyl-tRNA synthetases (ARSs) are a group of enzymes responsible for the first step of protein translation. Among them, the KARS1 gene encodes lysyl-tRNA synthetase 1, an enzyme essential for charging tRNA-Lys with lysine in both the cytoplasm and mitochondria. Mutations in KARS1 are associated with a wide range of clinical phenotypes, including leukoencephalopathy, hereditary deafness, peripheral neuropathies, and multisystemic involvement. METHODS: We hereby report a detailed case study of a 15-month-old boy presenting at age 5 months with developmental delay, microcephaly, hypotonia, sensorineural deafness, retinopathy, visual impairment, nystagmoid eye movements, and hepatic and immuno-hematological abnormalities. In addition, he exhibited a severe hyperkinetic movement disorder, not previously reported in the literature, and developed epilepsy at 13 months. Genetic testing identified two rare compound heterozygous variants in the KARS1 gene. RESULTS: With this report, we aim to contribute to the expanding of both the clinical phenotype and the allelic spectrum of lysyl-tRNA synthetase-related disorders. Our study also includes a review of previously described KARS1 cases presenting with movement disorders. CONCLUSIONS: Our findings further highlight the importance of assessing systemic involvement and performing brain and spinal neuroimaging, as well as implementing genetic screening, in infants presenting with global developmental delay, sensory deficits, and movement disorders-features that may suggest a mitochondrial disorder such as those involving ARS mutations.