A Case of Alpers–Huttenlocher Syndrome Due to a New POLG1 Mutation with Rapid Onset of Partial Status Epilepticus: Serial Neuroradiological and Neurophysiological Evaluation

Abstract

Alpers–Huttenlocher syndrome (AHS) is a severe and progressive neurodegenerative disease caused by mutations in the gene encoding the catalytic subunit of the mitochondrial-DNA-specific polymerase-γ (POLG1) gene. The primary features of AHS include refractory seizures, developmental regression, and hepatopathy, but these features may have varying degrees of severity and time of onset. Electroencephalogram (EEG) typically shows occipital lobe predilection, and progressive cortical atrophy with signal abnormalities and diffusion-weighted imaging (DWI) cortical-restricted diffusion are reported on brain magnetic resonance imaging (MRI). These findings may not occur or may arise later in the course of the disease, preventing early diagnosis of AHS. We describe a new case of AHS in a 6-year old-girl that evolved from a rapid onset myoclonic status into epilepsia partialis continua, with continuous multifocal asynchronous myoclonus and carrier of a de novo heterozygous mutation in POLG1 gene. EEG, MRI, and polygraphic changes that occurred during the first 3 months of the disease, and the clinical evolution during a 3-year follow-up period are described. EEG 1 month after onset documented rhythmic high-amplitude delta with superimposed polyspikes followed by progressive flattening of background activity. Brain MRI initially mimicked an immune-mediated encephalitis; within 3 months after onset, multifocal cortical signal abnormalities, diffuse cortical atrophy, and marked lactate peak suggested AHS syndrome. Epilepsy, which was initially drug-resistant, ceased 11 months later. After 3 years of follow-up, she still needs close medical support. Conclusion Our case provides new mutation in POLG1 gene not described previously. We suggest detailed information in a case of AHS on temporal evolution of MRI and EEG patterns that may represent different stages of the disease course. Early identification of these patterns and their clinical correlates may provide insight into the pathogenetic mechanisms of the disease progression and help define diagnostic and therapeutic approaches.