Chorea-Acanthocytosis: From Motor to Behavioral and Olfactory Profiles.

BACKGROUND

Chorea-acanthocytosis (ChA) clinically presents with motor and non-motor symptoms. Some features of the disease and their intercorrelations have remained insufficiently characterized. Thus, we aimed to perform a multidimensional assessment of ChA patients, focusing on motor, behavioral, cognitive and olfactory domains.

METHODS

A cross-sectional clinical assessment of 23 genetically confirmed ChA patients was conducted from 2022 to 2024. Patients were evaluated using the Unified Huntington's Disease Rating Scale (UHDRS) and Mini-Mental State Examination. A case-control comparison of olfactory function was also performed between eligible patients (n = 20) and age-and gender-matched controls (n = 20) using the Sniffin' Sticks test.

RESULTS

The mean age and disease duration were 38.57 ± 7.26 years and 7.86 ± 6.04 years, respectively. Chorea (91.3%), dystonia (82.6%) and oculomotor abnormalities (78.3%), particularly impaired vertical saccades and smooth pursuit, were frequent. All patients exhibited at least one behavioral disorder, most commonly anxiety, mood disorders (including sad mood and low self-esteem) and obsessive-compulsive features. Suicidal thoughts were found in 21.7% of the patients. Among patients with preserved cognition, 50% demonstrated hyposmia (sum of odor identification, discrimination and threshold scores [TDI] < 30.75), with significantly reduced odor discrimination, identification and TDI scores versus controls. Disease duration was negatively associated with olfactory function. Higher UHDRS motor scores were associated with poorer olfactory, cognitive and functional outcomes.

CONCLUSION

These findings demonstrated the varied manifestations of ChA, identifying olfactory impairment as a prevalent, underrecognized non-motor symptom, with potential implications for clinical evaluation and management. Further multicenter studies with larger cohorts are required to confirm these observations and clarify their prognostic value.