Novel POLG variants associated with late-onset de novo status epilepticus and progressive ataxia

Mitochondrial disease is phenotypically and genetically heterogeneous with an estimated prevalence of 1 in 4,300. Mutations in the POLG gene, encoding the catalytic subunit of DNA polymerase gamma, are an important cause of mitochondrial disease. The spectrum of clinical manifestations in POLG-related mitochondrial disease is variable, with disease onset ranging from adulthood-onset dominant or recessive progressive external ophthalmoplegia (chronic progressive external ophthalmoplegia), ataxia-neuropathy spectrum, myoclonic epilepsy, myopathy, and sensory ataxia to childhood-onset Alpers syndrome, which is characterized by intractable seizures, psychomotor regression, and hepatic impairment. Epilepsy is a poor prognostic factor in POLG mutations, and the onset of epilepsy often clusters in childhood (,5 years) and teenage. However, late-onset epileptic encephalopathy is uncommon. Herein, we describe a patient who died of de novo, late-onset refractory status epilepticus with the identification of 2 novel variants in the POLG gene.