Clinical and genetic findings of three patients with chorea-acanthocytosis

Introduction: Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in the VPS13A gene, encoding chorein, a protein involved in membrane homeostasis. Case report and methods: Three clinical cases are described. The first, a 36-year-old man, presented with hyperkinetic movements, seizures, psychiatric symptoms, and caudate atrophy. Genetic testing revealed a homozygous splice-site mutation (c.9276–2 A> T) in VPS13A. The second case involved a patient with a milder phenotype but typical ChAc features, except epilepsy. A homozygous deletion which includes exons 69 and 70 was identified. This deletion is absent from control population databases and is described for the first time. Her younger brother, complaining of hyperCKemia and involuntary movements, was tested and identified as a homozygous carrier of the same deletion. Conclusions: ChAc should be considered in case of patients featuring a plethora of diffuse symptoms showing multisystemic involvement. Comprehensive genetic testing in patients with complex neurological symptoms might improve diagnostic accuracy and enhance knowledge of genotype-phenotype correlations in ChAc.