Acute neuro-inflammatory presentation of ATP1A3 variants: Case reports of three patients with different phenotypes.
TL;DR
Three patients with ATP1A3 variants who presented with initial acute encephalopathy, an unusual presentation, are described to draw clinicians' attention to this lesser-known clinical presentation.
Abstract
Background
ATP1A3 variants are responsible for rare neurological conditions such as Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP), and Cerebellar Ataxia Areflexia Pes Cavus Optic Atrophy and Sensorineural Hearing Loss (CAPOS). Intermediate phenotypes include Relapsing Encephalopathy with Cerebellar Ataxia (RECA) and Fever-induced Proximal Weakness and Encephalopathy (FIPWE). Acute encephalopathy as a clinical presentation is unusual. We describe three patients with ATP1A3 variants who presented with initial acute encephalopathy, an unusual presentation, to draw clinicians' attention to this lesser-known clinical presentation. CASE PRESENTATIONS In all these cases, encephalitis, Guillain-Barré syndrome, or rhombencephalitis with ataxia were initially suspected, despite normal MRI and cerebrospinal fluid (CSF) findings. Ultimately, genetic analyses identified an ATP1A3 variant, including Arg756 variants in 2 cases. The first case is a 11-year-old girl with rapid-onset tetraparesis, facial diplegia, dysarthria, dysphagia, and dystonia, with a final diagnosis of RDP. The second patient is a 21-month-old boy who presented with acute cerebellar ataxia, weakness and areflexia, relapsing two times after viral infections. Final diagnosis was RECA. The third patient is a 3-year-old boy who presented with acute quadriplegia, dysarthria, dysphagia, and seizures. Final diagnosis was AHC.
Conclusion
When patients present with a picture of autoimmune encephalitis or polyradiculoneuritis with normal imaging and CSF analysis, and no response to standard anti-inflammatory treatment, a search for ATP1A3 gene mutations should be considered.