Acute Necrotizing Encephalopathy of Childhood Associated with Primary Infection of HHV 6: An Important Differential Diagnosis of Mitochondrial Diseases

Background: Acute necrotizing encephalopathy of childhood (ANEC) is a rare, febrile encephalopathy due to neurotropic viral infection causing rapid alteration of consciousness and seizures. In cranial magnetic resonance imaging (cMRI), symmetrical involvement of the thalami is characteristic, as is absence of pleocytosis and increased protein level in cerebrospinal fluid (CSF).

Case Report: We report on a previously healthy, 12-month-old Turkish toddler presenting with an upper respiratory infection followed by fever, prolonged impaired consciousness, movement disorder, and generalized seizures. Laboratory results showed lactic acidosis, normal inflammatory parameters, transaminases and elevated CSF proteins without pleocytosis. Cranial MRI revealed increased T2-signal intensity with impaired diffusion in the thalami. Suspecting mitochondrial disease biochemical analysis of skeletal muscle tissue was performed showing normal activity for respiratory chain complexes (RCC) I-IV. Functional analysis of mitochondria revealed slight deficiency of RCC II and III; whole-exome-sequencing was performed, showing no pathological mutation in any known mitochondriopathy-associated gene. Further diagnostics showed an active HHV-6-infection with seroconversion and increasing HHV-6-DNA titers in CSF confirming the suspected differential diagnosis of HHV-6 triggered ANEC. After ganciclovir treatment for 21 days, the patient showed complete recovery. A follow-up cMRI after 4 weeks showed improvement of the cerebral lesions.

Conclusion: In western countries, ANEC is a rare disease of unknown pathogenesis. It should be considered as a differential diagnosis of mitochondrial encephalopathies. Identification of the underlying agent and early antiviral treatment may improve the outcome. Normal transaminases might be positive predictors for a more favorable course of the disease.