Martin Paucar ^1,2* Josephine Wincent ^3,4 Charlotta Rubin ² Kevin Peikert ^5,6 Josefin Kyhle ⁷ Stellan Hertegård ^8,9 Riita Möller ^10,9 Soheir Beshara ^11,12 Per Svenningsson ^1,13

• ¹ Department of Clinical Neuroscience, Karolinska Institutet (KI), Stockholm, Sweden
• ² Karolinska University Hospital, Huddinge, Stockholm, Sweden
• ³ Clinical Genetics, Department of Molecular Medicine and Surgery, Karolinska Institutet (KI), Solna, Stockholm, Sweden
• ⁴ Department of Clinical Genetics, Karolinska University Hospital, Huddinge, Stockholm, Sweden
• ⁵ Department of Neurology, University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany
• ⁶ Center for Transdisciplinary Neurosciences Rostock, Center for Medical Research, University Hospital Rostock, Rostock, Mecklenburg-Vorpommern, Germany
• ⁷ Department of Speech and Language, Karolinska University Hospital, Stockholm, Spain
• ⁸ Department of Clinical Science, Intervention and Technology, Karolinska Institutet (KI), Solna, Stockholm, Sweden
• ⁹ Department of Otolaryngology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
• ¹⁰ Department of Medical Biology and Biostatistics, Karolinska Institutet (KI), Solna, Stockholm, Sweden
• ¹¹ Department of Molecular Medicine and Surgery, Karolinska Institutet (KI), Solna, Stockholm, Sweden
• ¹² Department of Clinical Chemistry, Karolinska University Hospital, Huddinge, Stockholm, Sweden
• ¹³ Department of Neurology, Karolinska University Hospital, Huddinge, Stockholm, Sweden

The diseases historically known as neuroacanthocytosis (NA) conditions include VPS13A disease (formerly chorea-acanthocytosis) and XK disease (formerly McLeod syndrome). Here we report a patient with a hyperkinetic syndrome associated with variants in VPS13A with a concomitant homozygous nucleotide expansion in Replication factor C, subunit 1 (RFC1) and evaluate the role of ektacytometry for the assessment of acanthocytes.Investigations included clinical assessments, neuroimaging studies, laboratory analyses, blood smears, ektacytometry, psychometric evaluation, and genetic analyses. Using ektacytometry, an osmoscan curve is obtained yielding a diffraction pattern as a measure of average erythrocyte deformability from circular at rest to elliptical at a high shear stress. The pattern allows the derivation of several parameters (mainly EI-max, O-min and O-Hyper points). Samples from two other patients with genetically proven VPS13A disorder and XK disease and varying numbers of acanthocytes as well as from a fourth with acanthocytosis due to liver failure were also analyzed.The patient has impulsivity, chorea and disabling feeding dystonia refractory to treatment and 15% acanthocytes in peripheral blood. Genetic workup revealed compound heterozygous variants c.1732_1733del; p.(V578Ffs*9) and c.8282C>A, p.(S2761*) in VPS13A with absence of chorein in the blood, the latter variant is novel. In addition, he harbors a homozygous nucleotide expansion in the RFC1 gene, reported in cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).However, the patient does not display ataxia yet. Ektacytometry revealed significantly reduced erythrocyte deformability in this patient and in another man with VPS13A disease. In contrast, the patient with XK disease had 2% acanthocytes and mild abnormalities on ektacytometry. In the three cases, ektacytometry yielded a specific pattern, different from acanthocytosis due to liver failure.