Clinicopathologic findings of CARS2 mutation

Publication date: Available online 4 July 2018
Source:Pediatric Neurology
Author(s): Debopam Samanta, Murat Gokden, Erin Willis
OBJECTIVESWe report a 13-year-old girl with a past medical history of epilepsy, intellectual impairment, dysphagia with gastric tube dependence, and autism spectrum disorder who presented with focal status epilepticus.METHODSVideo electroencephalogram showed left occipital pseudoperiodic epileptiform discharges and frequent seizures originating from the left hemisphere. The seizure was refractory to anti-epileptic medications and pharmacologic coma. Subsequently, left occipital lobectomy was done. Extensive workup including whole exome sequencing, histopathologic examination of brain and muscle samples, mitochondrial DNA content analysis of tissue sample was completed to detect the etiology.RESULTSSkeletal muscle mitochondrial DNA content (qPCR) analysis showed approximately 37% of the mean value of age and tissue matched controls consistent with a mitochondrial depletion syndrome. Microscopic examination of the brain showed cortical abnormalities that largely consisted of infarct-like pathology in a laminar manner, abnormalities of neuronal distribution, and white matter changes. Compound heterozygous mutations of the CARS2 gene were identified by whole exome sequencing; V52G variant [p.Val52Gly (GTG>GGG):c.155 T>G in exon 1] was inherited from the mother and T188M variant[p.Thr188Met (ACG>ATG): c.563 C>T in exon 5] was inherited from the father.CONCLUSIONThis is the first detailed clinicopathologic description of Alpers-Huttenlocher syndrome (AHS) phenotype from CARS mutations.



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