A Unique Case of Late Adult Onset Dyskinesia due to Adenylyl Cyclase 5 Mutation
Gunjanpreet Kaur1, Xiaoyi Gao2, Wilson Rodriguez1, Pratap Chand1
1Neurology, St. Louis University School of Medicine, 2Emory University School of Medicine
Background:
Adenylyl cyclase 5 (ADCY5)‐related movement disorder (ADCY5‐RMD) is a rare, childhood‐onset disease resulting from mutations in the ADCY5 gene. The molecular pathogenesis of ADCY5‐RMD involves perturbations in the striatal cAMP synthesis pathway which is involved in the fine regulation of movement execution. Clinical features of ADCY5-RMD include hyperkinetic movements, most commonly focal or generalized chorea, dystonia and myoclonus. Symptom onset typically ranges from 6 months to 10 years of age with isolated case reports of symptom onset as young as 2 months of age. We present a unique case of late adult -onset dyskinesia in a 79 year old male with ADCY5 mutation.
Design/Methods:
The clinical phenotype, laboratory tests, imaging and genetic testing are described.
Results:
A 79-year-old right-handed Caucasian male presented with painless involuntary movements starting in right foot and later spreading to feet, hands, tongue and jaw. His past medical history was significant for memory difficulties with normal laboratory tests for reversible dementia and neuroimaging including Magnetic resonance imaging and angiography of brain. He had COVID infection 2 years prior. The involuntary movements consisted of buccolingual and jaw dyskinesias, and choreiform movements of his hands and feet. No history of dopamine receptor blocking receptor drugs use. He was started on Valbenazine 40 mg daily and dyskinesias responded partly to the medication. The dyskinesias stopped completely when the dose was increased to 80 mg daily. All metabolic, toxic, autoimmune serum tests for causes of dyskinesia/dystonia were negative. Genetic testing by next generation sequencing comprehensive dystonia panel was positive for ADCY5 c2908_2910del (p.Phe970del).
Conclusions:
Late adult onset of movement disorders related to ADCY5 mutations has not been reported in the literature and we are unsure what precipitated the manifestation so late in our patient. There are reports of cognitive decline and tau deposits in an autopsied case.