4th Year Medical Student SUNY Upstate Medical University
This abstract has been invited to present during the Better Patient Outcomes through Diversity Platform poster session
Rationale: Polymerase Gamma 1 (POLG1) variants have been linked to epileptic disorders such as childhood Myocerebrohepatopathy Spectrum (MCHS) and Myoclonic Epilepsy Myopathy Sensory Ataxia (MEMSA) via the effect on mitochondrial DNA integrity. Human Herpes Virus-6 (HHV-6) is the cause of Roseola Infantum or “sixth disease,” a predominantly childhood-based illness characterized by upper respiratory symptoms followed by a sudden high fever and rash. HHV-6 has the ability to infiltrate host DNA and can inhibit mitochondrial function and impair cellular homeostasis. These effects could be heightened in patients with predisposing conditions including POLG 1 variants. Most children are expected to make a full recovery from HHV-6 infection, which is an important cause of meningoencephalitis in young children. Recently, POLG1 variants have been implicated in fatal HHV-6 encephalitis in previously healthy young boys who were found to be compound heterozygotes for POLG1 variants. Methods: A previously healthy, developmentally normal two-year-old boy contracted HHV-6 meningoencephalitis. The patient had a CSF study showing pleocytosis and a follow-up CSF study that then demonstrated elevated proteins as well. Lactate and neurotransmitters on CSF testing were normal. His EEG showed migrating focal seizures and MRI showed DWI changes consistent with the focalities seen on EEG. Along with antiepileptic drugs, the patient received two rounds of IV solumedrol which resulted in improved mental status and decreased irritability. He subsequently underwent a long steroid taper.
Results: An autoimmune encephalitis panel including NMDA receptor antibodies was negative. Triad genetic testing revealed a de novo p.Ala467Thr variant in POLG1, a missense mutation known to decrease polymerase functioning. The now three-year-old patient continues to suffer from intractable seizures, mild right sided hemiparesis and expressive language difficulties. Conclusions: Our case presents a previously healthy boy with HHV-6 who had a severe course resulting in a movement disorder and refractory migrating epilepsy that was initially suspicious for an autoimmune (NMDA) encephalitis. The epilepsy gene panel was surprising in showing a single pathogenic de novo POLG1 variant. Heterozygous POLG1 variants have yet to be documented as disease causing in children. Our patient suggests that a single variant in POLG1 has the potential to cause a more severe presentation of an otherwise benign disease. An alternative diagnostic possibility is an atypical, antibody-negative Acute Disseminated Encephalomyelitis triggered by HHV-6, with the heterozygous POLG1 variant being an incidental finding. Funding: Please list any funding that was received in support of this abstract.: N/A