Pt459, a boy with lactic acidosis, developmental delays, hypertrophic cardiomyopathy, seizure, and combined complex deficiencies (I and IV), harbored the compound heterozygous mutations c.1343T>A (p.V448D) and c.953T>C (p.I318T) in KARS. KARS is a lysyl-transfer RNA synthetase that produces 2 proteins that localize to the cytosol and mitochondria. Here, KARS1 is linked to lactic acidosis.