Genetics
Mutations in the ATP1A3 gene (ATPase Na + /K + transporting subunitalpha3), encoding an ionic pump, are a cause of rapid-onset dystonia-parkinsonism (RDP)¹.
The Na/K-ATPase pump exchanges Na+ for K+ through ATP hydrolysis and is therefore a major determinant of resting membrane potentials. In the brain, the a3-subunit (encoded by ATP1A3) is exclusively expressed in neurons, particularly GABAergic neurons of the basal ganglia and cerebellum².

Mode of Inheritance
RDP is inherited in an autosomal dominant manner with reduced penetrance.

Clinical Presentation
The disorder typically presents in adolescence or young adulthood over a period ranging from several hours to weeks.

The acute onset is usually associated with a trigger such as fever, physical exertion, or emotional stress. Dystonic symptoms frequently show a rostro-caudal gradient with a strong involvement of the bulbar region, sometimes with laryngeal involvement, and are often accompanied by bradykinesia as a parkinsonian feature.

In addition, mutations in ATP1A3 have also been linked to a variety of clinical syndromes (pleiotropy) including epileptic or hemiplegic attacks (alternating hemiplegia of childhood), ataxia, cognitive decline, and other neurological disorders, often with a more severe course and an earlier age at onset.

Treatment
Symptoms usually only respond slightly to levodopa but also to benzodiazepines.