Phosphatidylethanolamines are the main lipid class altered in red blood cells from patients with VPS13A disease/chorea-acanthocytosis

Background VPS13A disease (chorea-acanthocytosis) 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 bulk 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 on 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 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.