Stroke-like Lesion and Status Epilepticus in a Child With NARS2-Related Combined Oxidative Phosphorylation Deficiency 24

Song SuWandong HuYong LiuQiong Lang^*Hongwei Zhang^*

• Children's Hospital Affiliated to Shandong University, Jinan, China

The NARS2 gene encodes mitochondrial asparaginyl-tRNA synthetase, and biallelic variants in NARS2 have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24), an autosomal recessive mitochondrial disorder characterized by highly heterogeneous clinical manifestations. This study retrospectively analyzed the clinical and genetic features of a Chinese infant presenting with status epilepticus and investigated the potential genotype–phenotype correlation. The proband, a 9-month-old girl, exhibited global developmental delay, increased muscle tone, elevated serum lactate and myocardial enzyme levels, and a brain magnetic resonance imaging (MRI) revealed focal cerebral lesion consistent with a metabolic or stroke-like infarction and delayed myelination. Whole-exome sequencing identified compound heterozygous NARS2 variants, including a large exon 6–11 deletion and a novel missense variant c.467T>C (p.Leu156Ser), inherited in an autosomal recessive manner. Both variants were absent from population databases and previously published literature. Notably, cerebral infarction has not been reported in any prior NARS2-related cases, suggesting a potential expansion of the clinical spectrum. Review of published NARS2 variants indicates that missense and loss-of-function mutations can lead to variable disease severity depending on residual enzyme activity. In summary, this case broadens the phenotypic and mutational spectrum of NARS2-related COXPD24 and highlights the importance of considering large exon deletions and novel variants in patients with early-onset mitochondrial encephalopathy and epileptic phenotypes.