Case report: Neuroacanthocytosis associated with novel variants in the gene with concomitant nucleotide expansion for CANVAS and assessment with osmotic gradient ektacytometry.

BACKGROUND AND OBJECTIVES

The diseases historically known as neuroacanthocytosis (NA) conditions include disease (formerly chorea-acanthocytosis) and disease (formerly McLeod syndrome). Here we report a patient with a hyperkinetic syndrome associated with variants in with a concomitant homozygous nucleotide expansion in Replication factor C, subunit 1 () and evaluate the role of ektacytometry for the assessment of acanthocytes.

METHODS

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 disorder and disease and varying numbers of acanthocytes as well as from a fourth with acanthocytosis due to liver failure were also analyzed.

CASE PRESENTATION

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.(V578Ffs9) and c.8282C > A, p.(S2761) in with absence of chorein in the blood, the latter variant is novel. In addition, he harbors a homozygous nucleotide expansion in the 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 disease. In contrast, the patient with 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.

CONCLUSION

Pathogenicity of the variants is confirmed by absence of chorein, long-term follow up is required to evaluate any synergistic impact of for the underlying CANVAS mutation. New generation ektacytometry provides an objective measurement of erythrocytes' rheological properties and may serve as a complement to blood smears. Finally, ektacytometry's ability to detect deformability of erythrocytes in NA seems to depend on the degree of acanthocytosis.