LAUSR

A 38-year-old Caucasian female presented with 2 years of progressive involuntary movements, dysarthria, sialorrhea, dysphagia, gait impairment, and restlessness. She denied prior use of neuroleptics. Levodopa (400 mg/day), glycopyrrolate, pro-pranolol (40 mg/day), clonazepam (2 mg/day), diazepam (5 mg/day), and deutetrabenazine (24 mg/day, limited by seda-tion) were prescribed without improvement. Examination showed sialorrhea, dysarthria, hypophonia, gen-eralized chorea, and dystonia. Deep tendon re fl exes were absent at the ankles. Her gait was characterized by intermittent “ head drop ” with ballistic fl exion of the neck and periodic left foot inversion with plantar fl exion (Video Segment 1). Laboratory investigations revealed an increased total creatine kinase 205 U/L (normal, 32 – 182 U/L). Peripheral blood smear did not demonstrate acanthocytes. Liver enzymes were normal. Whole genome sequencing showed a pathogenic variant in VPS13A (c.9109C > Tp.Arg3037) and a second variant (c.9497C > Ap.Arg3158Arg). This latter variant was interpreted as being of unknown signi fi cance; however, pathogenicity was supported at the PM 2 ( “ pathogenic moderate 2 ” ) level and by her presentation, which was consistent with chorea-acanthocytosis (ChAc).