Puerto Rican family cohort presenting with rapid-onset dystonia-parkinsonism due to an ATP1A3 Pathogenic Variant (2188)

Objective: To describe a Puerto Rican family with three affected members with an ATP1A3 pathogenic variant that presented with the rapid-onset dystonia-parkinsonism phenotype. Background: Na+/K+-ATPase is an ubiquitous, transmembrane enzyme that is crucial in creating and maintaining the gradients for Na+ and K+ across cell membranes of different cell types. The alpha subunit is the catalytic subunit, of which four isoforms exist. Three of the four alpha isoforms (alpha1,2, and 3) are expressed in the nervous system. Mutations affecting the alpha3 subunit, ATP1A3, expressed in neurons, has been associated to several well-characterized clinical phenotypes: Rapid-onset dystonia-parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss). Design/Methods: We describe a family with three affected members with the ATP1A3 c.2267G>A(R756H) pathogenic variant who presented with the rapid-onset dystonia-parkinsonism phenotype. Results: Retrospective review of a family (two siblings and their mother) with ATP1A3 pathogenic variant (n=3). In all of the three affected members, same pathogenic variant found(c.2267G>A(R756H). Age of onset of all patients during childhood. Patient IIa and IIb were ten years old and five years old respectively. All patients presented rapid onset of symptoms triggered by fever. Bulbar symptoms were the most prominent symptom with dysarthria, mutism, and dysphonia. A rostrocaudal gradient of dystonia and parkinsonism were observed in 100% of the patients. Trial of levodopa-carbidopa was given to 75% of patients (IIa and IIb) without response. Symptomatic relief of dystonia seen with benzodiazepine trial. Conclusions: Rapid-onset dystonia-parkinsonism phenotype is well described in the literature by the abrupt onset of bulbar symptoms and rostrocaudal gradient of dystonia and parkinsonism. We report a family with ATP1A3 pathogenic variant. To our knowledge this is the first family reported in Puerto Rico. It is imperative to create awareness to consider genetic testing in a patient with abrupt onset, rostrocaudal gradient dystonia, and prominent bulbar findings. Disclosure: Dr. Montalvo Acevedo has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Diaz Diaz has nothing to disclose. Dr. Montalvo has nothing to disclose. Dr. Gonzalez Montes has nothing to disclose. Dr. Bolo-Diaz has nothing to disclose. Dr. Rodriguez Hernandez has nothing to disclose. Dr. Vazquez has nothing to disclose.