Objective: Here we report two patients with genetically confirmed neuroacanthocytosis (NA) and expand the role of ektacytometry for the assessment of acanthocytes.

Background: The main NA syndromes include VPS13A-related disorders (formerly chorea-acanthocytosis) and McLeod’s syndrome (MLS). Acanthocytes are assessed by the blood  smear protocl proposed by Storch et al, The functional properties of red blood cells membranecan can be measured by ektacytometry using a laser optical rotational red cell analyzer (Lorrca® Maxsis, RR Mechatronics) when erythrocytes are subjected to solutions with various osmolality.

Method: Investigations included clinical assessments, neuroimaging studies,blood smears, ektacytometry, laboratory and genetic analyses. Six points can be yielded from ektacytometry; O-min: giving information about surface/volume ratio, EI: for maximal deformability, O-hyper: osmolality in the hypertonic region giving information about hydration status of the cells, O-max: osmolality at maximal elongation and AUC: total area under the curve.

Results: Patient 1 has impulsivity, chorea and aevere feeding dystonia refractory to treatment. He carries the compound heterozygous variants c.1732_1733del; p.V578Ffs*9 and c.8282C>A, p.S2761X in VPS13A with absence of chorein in his blood. In addition, he has a homozygous nucleotide expansion in the RFC1 gene which is mutated in CANVAS but does not display ataxia yet. Patient 2, with epilepsy and neuromuscular symptoms, carries a de novo heterozygous nonsense variant c.397C>T; p.R133X in XK. In both cases caudate atrophy was detected whereas cardiac evaluation was unremarkable. Deformability in erythrocytes was significantly reduced in patient 1 who has 15% acanthocytosis, patient 2 in contrast has mild abnormalities and 2% acanthocytes. In both cases ekatocytometry showed a shift of the ‘O hyper’ point only. In contrast, acanthocytosis due to alcoholic liver failure yielded a completely different curve.

Conclusion: Pathogenicity of the VPS13A variants is confirmed by absence of chorein in patient 1. Sporadic pathogenic variants in XK are rare. Ektacytometry provides an objective measurement compared to the subjective cell count under the microscope and reveals a ‘finger print’ for each membrane defect.  Ektacytometry’s performance to detect deformability of erythrocytes in NA seems to depend on the degree of acanthocytosis. The method is a useful complement to the Storch protocol in cases with low degree of acanthocytosis.

References: Walker RH, Peikert K, Jung HH, Hermann A, Danek A. Neuroacanthocytosis Syndromes: The Clinical Perspective. Contact (Thousand Oaks). 2023 Dec 10;6:25152564231210339. doi: 10.1177/25152564231210339. PMID: 38090146; PMCID: PMC10714877.

Storch A, Kornhass M, Schwarz J. Testing for acanthocytosis A prospective reader-blinded study in movement disorder patients. J Neurol. 2005 Jan;252(1):84-90. doi: 10.1007/s00415-005-0616-3. PMID: 15654559.

Lazari D, Freitas Leal JK, Brock R, Bosman G. The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease. Front Physiol. 2020;11:288. doi: 10.3389/fphys.2020.00288. PMID: 32351399; PMCID: PMC7174766.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ektacytometry-in-neuroacanthocytosis/