BACKGROUND: VPS13A disease is an ultra-rare disorder caused by loss of function mutations in VPS13A characterized by striatal degeneration and by red blood cell (RBC) acanthocytosis. VPS13A is a bridge-like protein mediating lipid transfer at membrane contact sites.

OBJECTIVES: To assess the lipid composition of patient-derived RBCs.

METHODS: RBCs collected from 5 VPS13A disease patients and 12 control subjects were analyzed by mass spectrometry (lipidomics).

RESULTS: While we found no significant differences in the overall lipid class level, alterations in certain species were detected: phosphatidylethanolamine species with both longer chain length and higher unsaturation were increased in VPS13A disease samples. Specific ceramide, phosphatidylcholine, and sphingomyelin species were also altered.

CONCLUSIONS: The presented alterations of particular lipid species in RBCs in VPS13A disease may contribute to (1) the understanding of acanthocyte formation, and (2) future biomarker identification. Lipid distribution seems to play a key role in the pathophysiology of VPS13A disease. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.