COVID-19 Infection as a Possible Trigger for POLG-Related Mitochondrial Disease: A Case Report

A six-year-old child presented with an acute onset of refractory epileptic seizures during a coronavirus disease 2019 (COVID-19) infection. As her clinical condition progressed, she developed super-refractory status epilepticus, resulting in significant cognitive and motor impairments. Genetic analysis revealed a homozygous mutation in the DNA Polymerase Gamma, Catalytic Subunit (POLG) gene (c.1399G>A; p.Ala467Thr), confirming a diagnosis of Alpers-Huttenlocher syndrome. The clinical course was characterized by refractory seizures and developmental regression, and it ultimately culminated in liver failure and multiorgan dysfunction, resulting in death. This case underscores the critical importance of early genetic evaluation in children with unexplained refractory seizures, particularly for detecting underlying mitochondrial disorders such as POLG-related syndromes. Mitochondrial function is highly sensitive to physiological and environmental stressors, including viral infections. Pathogens such as hepatitis viruses, influenza virus, HIV, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate mitochondrial dysfunction. Therefore, identifying genetic vulnerabilities in these patients is essential for optimizing management strategies and potentially mitigating rapid clinical decline.