DARS1 and Encephalopathy: Although genetic defects in two other cytosolic aaRSs, namely, DARS1 and RARS1, also cause HLD10,81,82, defects in at least ten cytosolic aaRSs cause distinct neurologic disorders including encephalopathy, microcephaly, as well as peripheral neuropathy1,11, suggesting that aaRS inhibition of protein synthesis is unlikely to be the principal etiology underlying HLD.