Perrault Plus Syndrome Due to the LARS2 Variant c.457A>C Manifesting With Epilepsy, Cognitive Impairment, Myopathy, Spastic Tetraparesis, and Deafness: A Case Report

To our knowledge, this is the first carrier of the homozygous variant c.457A>C in LARS2 who has not only Perrault syndrome but also additional neurological symptoms. The patient is a 35-year-old man with a history of sensorineural hearing loss since birth, rare generalized tonic-clonic seizures, progressive gait disturbance and cognitive decline since the age of 33, and spasticity since the age of 34. Examination of his symptoms revealed a multisystem mitochondrial disorder due to the c.457A>C variant in LARS2, which manifested phenotypically as leukodystrophy, cognitive impairment, epilepsy, hearing loss, myopathy, and spastic tetraparesis. The patient benefited from drug treatment with levetiracetam (1000 mg/day) and a vitamin cocktail. In summary, this case suggests an association between the homozygous variant c.457A>C in LARS2 and a severe, adult-onset, neurologic phenotype including leukoencephalopathy, cognitive decline, progressive spastic tetraparesis, myopathy, and epilepsy within the expanding LARS2 spectrum. Physicians should be aware that LARS2 variants can manifest as a multisystem disorder and not just as Perrault syndrome.