Rapid-Onset Dystonia-Parkinsonism Presenting as Tremor-Dominant Parkinson's Disease (P04.161)

OBJECTIVE: To describe a previously unidentified phenotype of rapid-onset dystonia-parkinsonism (RDP) with characteristic features of idiopathic Parkinson9s disease (PD), including levodopa-responsive rest tremor. BACKGROUND: RDP is caused by mutations of the ATP1A3 gene which encodes the α3 subunit of Na + /K + ATPase. The most common presentation of RPD is rostrocaudal onset of levodopa-unresponsive limb dystonia, bradykinesia, postural instability, and bulbar dysfunction which develop within hours or days of a physiologic trigger, such as stress, physical exertion, or alcohol consumption. Rest tremor is not typical. DESIGN/METHODS: We discuss a 61 year old man who presented with rest tremor of his right leg and arm, followed within 2 days by right body dystonia and within 2 months by dysphonia and cervical dystonia. On initial exam he had a UPDRS-III score of 43 with a grade 1 rest tremor in his right arm and leg. His tremor and bradykinesia were subjectively and objectively levodopa-responsive. Blinded review of the patient9s videotaped examination by an independent movement disorders expert yielded a diagnosis of idiopathic PD. RESULTS: Given the patient9s rapid symptom progression, he was tested for RDP and found to possess an unreported ATP1A3 mutation. Neuropsychological testing was consistent with our RPD cohort, demonstrating executive function impairment. DTI imaging revealed decreased integrity in cerebellothalamic circuitry, also consistent with our cohort compared to controls. CONCLUSIONS: Our patient differed from typical RDP in several respects: 1) Presentation with a levodopa-responsive rest tremor characteristic of idiopathic PD, 2) a later age of onset compared to most RDP kindreds, and 3) absence of an identifiable trigger. On database review two other RDP patients also had a rest tremor but did not otherwise display a PD phenotype. We suggest that testing for RDP should be considered more routinely in syndromes which closely resemble idiopathic PD, if the symptoms progress quickly over days to weeks. Disclosure: Dr. Tate has nothing to disclose. Dr. Brashear has received personal compensation for activities with Allergan Inc, Xenoport, and Ipsen as a consultant. Dr. Brashear has received personal compensation in an editorial capacity for book royalties. Dr. Whitlow has nothing to disclose. Dr. Snively has nothing to disclose. Dr. Ozelius has nothing to disclose. Dr. Sweadner has received personal compensation for activities with the University of Toledo, University of Puerto Rico and University of Toledo, as a consultant and speaker. Dr. Sweadner has received personal compensation in an editorial capacity for Journal of Biological Chemistry and American Journal of Physiology Cell Physiology. Dr. Stacy has received personal compensation for activities with Allergan, Inc., Chelsea, General Electric, GlaxoSmithKline, Inc., Merck, Merz Pharma, Neuronova, Novartis, Noven, Osmotica, SK Life Sciences, Teva Neuroscience, and UCB Pharma. Dr. Stacy has received research support from Cergene, Impax Pharmaceuticals, the Michael J. Fox Foundation, the National Institutes of Health, Novartis, the Parkinson Study Group, EMD Serono, Merck, and Neuraltus. Dr. Haq has nothing to disclose.