ICNC Abstracts, ICNC 2018

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Novel homozygous mutations in NARS2 gene with mitochondrial dysfunction presenting as early infantile epileptic encephalopathy
Wilson Heredia

Last modified: 2018-09-09



NARS2 is a gene that encodes for an aminoacyl-tRNA synthetase, enzymes that play a crucial role in protein biosynthesis. While the protein is encoded by the nuclear genome, it is imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutation in this gene have been previously associated with COXPD24. We report novel variants in the NARS2 gene presenting as early infantile epileptic encephalopathy.


Exome testing identified compound heterozygous mutations in the NARS2 gene. Autopsy of brain, muscle and cardiac tissue was performed for functional confirmation of pathogenicity.

Case description

A 3-month-old girl presented with acute onset focal seizures, episodes of epilepsia partialis continua and myoclonic seizures. Exam revealed opthalmoplegia. During hospitalization, she developed rapidly progressive hypertrophic cardiomyopathy and cardiac failure. Due to progressive cardiac decline and intractable epilepsy, care was redirected. Exome testing revealed a compound heterozygous mutation in NARS2 gene. Autopsy confirmed left ventricular hypertrophy with massively increased numbers of pathologic appearing mitochondria. Skeletal muscle biopsy showed abnormal COX staining and analysis of respiratory chain function revealed significantly decreased complex IV activity. Brain biopsy showed an Alper’s type histology with punched out neuropil vacuolation in a Leigh’s disease type distribution (Pallidum, thalamus, midbrain tectum and pontine tegmentum).


Here we present a novel mutation in the NARS2 gene with an atypical clinic-pathological presentation. Functional


NARS2; Infantile epileptic encephalopathy

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