Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation

Abstract

Sir, we read with great interest the report describing 12 patients presented with early onset severe neurological disease, characterized by unique MRI features of leukoencephalopathy involving the thalamus and brainstem with high lactate (LTBL; Steenweg et al., 2012). Clinically, the patients fell into two distinct groups. Four patients showed a severe progressive psychomotor regression soon after birth followed by complex irreversible neurological features, however, all patients were alive up to 7 years of age. Eight patients had mild spasticity, seizures and irritability between 6 and 12 months of life with improvement of both clinical and MRI signs in the second year. Stereotypical brain MRI appearances led to molecular diagnosis of mutations in the mitochondrial glutamyl-tRNA synthetase ( EARS2 ) gene. An increasing number of mutations have been identified recently in genes involved in mitochondrial protein synthesis (Smits et al., 2010; Chrzanowska-Lightowlers et al., 2011; Rotig, 2011). Most of these gene defects result in histological [cytochrome c oxidase (COX) deficient or ragged red fibres] and biochemical (multiple respiratory chain defect) abnormalities in affected organs. The clinical phenotypes are usually early-onset, severe, and often fatal diseases, implying the importance of mitochondrial translation from birth. Although some have distinguishing features (Chrzanowska-Lightowlers et al., 2011; Rotig, 2011), as a group they form an overlapping spectrum of disease. The MRI features described by Steenweg et al. (2012) in patients with EARS2 mutations add characteristic radiological features to …