Phenotypic variability in sisters with VPS13A disease (chorea-acanthocytosis)

Abstract

Chorea-acanthocytosis (VPS13A disease) is a rare multisystem neurodegenerative disorder with a broad phenotypic spectrum. It is characterized by neuropsychiatric symptoms and the presence of acanthocytes. However, the relationship between acanthocytes and disease severity remains unclear. Diagnosis is established through genetic testing. We present two sisters with VPS13A disease, each exhibiting distinct clinical presentations. The younger presents with severe symptoms including drug-resistant epilepsy, neuropsychiatric issues, chorea, and self-mutilation, along with the presence of acanthocytes in her blood smear (10%). Genetic testing identified a homozygous synonymous mutation in the VPS13A gene (Chromosome 9: 79971783 G>C, exon 55, c.7806G>C, Pro2602=). Conversely, the older sister experiences only well controlled epileptic seizures and elevated creatine kinase levels, with no acanthocytes in peripheral blood smears, which have been performed three times. She also harbors the same homozygous synonymous mutation in the VPS13A gene. Our report highlights siblings with identical mutations but differing clinical presentations, emphasizing the variability in VPS13A disease manifestations. The younger sister has acanthocytosis and chorea, whereas the older did not demonstrate those features. The term “VPS13A disease” is proposed to encompass this group of diseases, acknowledging that acanthocytes or chorea may not always be present. Our findings support this terminological shift. Additionally, we first mentioned this synonymous mutation (NM_033305.3: c.7806G>C exon 55, p. Pro2602=) in the VPS13A gene, contributing to the understanding of this condition. © 2025 Elsevier B.V., All rights reserved.