[S3-1C-2] ATP1A3 mutations in alternating hemiplegia of childhood
In 2012, three independent groups discovered de novo heterozygous mutations in ATP1A3 for alternating hemiplegia of childhood (AHC). Mutations have been found in over 80% of the patients with AHC, most of which are missense mutations. ATP1A3 encodes the Na+/ K+-ATPase alpha 3 subunit, which is predominantly expressed in neurons in the brain. The movement of Na+ and K+ ions helps regulate the electrical activity of these cells and plays an important role in the signaling process that controls muscle movement. The activity of Na+/K+-ATPase also helps regulate cell size. Mutations in ATP1A3 have been found in patients with rapid-onset dystonia-parkinsonism (RDP), which shows an autosomal dominant pattern. In addition, mutations in ATP1A3 recently have been found in patients with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. The phenotype of ATP1A3-related neurologic disorders is expanding. However, the mutations associated with AHC are specifically localized in ATP1A3. Over 50% of the mutations in AHC have been found to be p.E815K and p.D801N. This presentation primarily discusses the ATP1A3 mutations associated with AHC.