Understanding the Pathophysiology of ATP1A3-Related Disorders

Abstract

The ATP1A3 gene encodes the alpha-3 subunit (α3 isoform) of Na⁺/K⁺ ATPase, a sodium-potassium pump primarily expressed in neurons and involved in maintaining neuronal membrane potential. Several genetic mutations in this gene have been identified and linked to a wide spectrum of phenotypes. These mutations and their phenotypes have been categorized into four ATP1A3-related disorders:

1. Alternating Hemiplegia of Childhood (AHC)

2. Rapid-Onset Dystonia Parkinsonism (RDP)

3. Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss (CAPOS)

4. Relapsing Encephalopathy with Cerebellar Ataxia (RECA)

This paper aims to provide a comprehensive overview of the pathophysiology of these four disorders.