PP05.8 – 2528: Early-onset mild type leukoencephalopathy caused by a homozygous EARS2 mutation

Abstract

Objective Mitochondrial diseases are a heterogeneous group of disorders resulting from primary dysfunction of the respiratory chain due to both nuclear and mitochondrial DNA mutations. Defective translation of mitochondrial DNA-encoded proteins, caused by mutations in either the mitochondrial or nuclear genomes, often manifest as severe infantile leukoencephalopathy. EARS2 is one of the newest members of nuclear mitochondrial disorders characterized by disturbed mitochondrial translation. This gene encodes the mitochondrial aminoacyl-tRNA synthetase specific for glutamate which is involved in mitochondrial DNA translation. Methods A patient is presented with an early onset, mild leukoencephalopathy which is caused by mutations in a single gene; EARS2. Results We report a 16 month-old girl, who was presented with a history of failure to walk. She achieved head control at 2 months and succeeded in sitting without support at 10 months. She was able to stand with support however she couldn't walk. Neurological findings were normal except failure to walk. Brain MRI revealed T2 and Fluid Attenuated Inversion Recovery (FLAIR) hyperintensity of the thalami, nucleus caudatus, putamen, midbrain, pons and cerebellar white matter. Periventricular and supraventricular white matter, corpus callosum and periaqueductal grey matter had T2 and FLAIR hyperintensity. Notably, periventricular rim, bilateral capsula interna and corona radiata were spared and had normal T2 signal. We sequenced the exons, intron-exon boundaries and promotor region of the EARS2 gene. We found homozygous mutation of the gene. Both of the maternal and paternal allele harboured a c.322C>T transition, predicting a p.R108W change. Conclusion We present a mild phenotype of EARS2 mutation, in addition to the reported cases of rapidly progressive disease with severe CNS involvement, which indicates particular mild phenotypes may remain under-diagnosed due to vague symptoms.