Choreoacanthocytosis, one of the forms of neuroacanthocytosis, is caused by mutations in vacuolar protein sorting-associated protein A (VPS13A), and is often misdiagnosed with other form of neuroacanthocytosis with discrete genetic defects. The phenotypic variations among the patients withVPS13Amutations significantly obfuscates the understanding of the disease and treatment strategies. In this study, two unrelated cases were identified, exhibiting the core phenotype of neuroacanthocytosis but with considerable clinical heterogeneity. Case 1 presented with an additional Parkinsonism phenotype, whereas seizures were evident in case 2. To decipher the genetic basis, whole exome sequencing followed by validation with Sanger sequencing was performed. A known homozygous pathogenic nonsense mutation (c.799C > T; p.R267X) in exon 11 of theVPS13Agene was identified in case 1 that resulted in a truncated protein. A novel missense mutation (c.9263T > G; p.M3088R) in exon 69 ofVPS13Aidentified in case 2 was predicted as pathogenic. In silico analysis of the p.M3088R mutation at the C-terminus of VPS13A suggests a loss of interaction with TOMM40 and may disrupt mitochondrial localization. We also observed an increase in mitochondrial DNA copy numbers in case 2. Mutation analysis revealed benign heterozygous variants in interacting partners of VPS13A such asVAPAin case 1. Our study confirmed the cases as ChAc and identified the novel homozygous variant ofVPS13A(c.9263T > G; p.M3088R) within the mutation spectrum ofVPS13A-associated ChAc. Furthermore, mutations inVPS13Aand co-mutations in its potential interacting partner(s) might contribute to the diverse clinical manifestations of ChAc, which requires further study.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00438-023-02032-2.