Alternating hemiplegia of childhood (AHC) [OMIM #614820] is a rare neurodevelopmental syndrome characterized by recurrent episodes of hemiplegia on alternating sides of the body, beginning in infancy. Hemiplegia episodes often resolve during sleep in affected individuals. Some patients may have specific triggers for hemiplegia, which may include cold temperatures, emotional stress, fatigue, and bathing. Other features include developmental delay, dystonia, choreoathetosis and epilepsy. Behavioral and psychiatric disorders may also be observed, including attention deficit, impulsivity, and short-temperedness. Mutations in ATP1A3 can also be associated with rapid-onset dystonia-parkinsonism [OMIM#128235].
Abnormalities of the ATP1A3 [OMIM #182350] gene, have been identified in patients with alternating hemiplegia of childhood. ATP1A3 has 23 coding exons and is located at 19q13.2. Heinzen et al. (2012) identified heterozygous ATP1A3 mutations in 82 out of 105 patients with AHC (78%), including missense, splice site and frameshift mutations. ATP1A3 encodes a subunit of the Na+/K+ ATPase pump, which is involved in maintaining electrochemical gradients across the plasma membranes of neurons. Functional studies of selected AHC-associated ATP1A3 mutations have shown that mutations lead to reduced ATPase activity in vitro.