Phenotypes and genotypes of mitochondrial aminoacyl-tRNA synthetase deficiencies from a single neurometabolic clinic.

Mitochondrial aminoacyl-tRNA synthetases play a major role in protein translation, synthesis, and oxidative phosphorylation. We reviewed all patients diagnosed with mitochondrial aminoacyl-tRNA synthetase deficiencies diagnosed in a single neurometabolic clinic. We report five patients with mitochondrial aminoacyl-tRNA synthetase deficiencies including , , , and deficiencies. Siblings with deficiency presented with global developmental delay within the first year of life. , , , and deficiencies were identified by whole exome sequencing. We report coagulation factor abnormalities in deficiency for the first time. We also report symmetric increased signal intensity in globus pallidi in FLAIR images in brain MRI in deficiency for the first time. One patient with deficiency had compound heterozygous variants in . One of those variants was an intronic variant. We confirmed the pathogenicity by mRNA studies. Mitochondrial aminoacyl-tRNA synthetase deficiencies are diagnosed by molecular genetic investigations. Clinically available non-invasive biochemical investigations are non-specific for the diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiencies. A combination of brain MRI features and molecular genetic investigations should be undertaken to confirm the diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiencies.