Testing for acanthocytosis A prospective reader-blinded study in movement disorder patients
Alexander Storch1, Markus Kornhass, Johannes Schwarz
1Dept. of Neurology, University of Ulm, 89081 Ulm, Germany. alexander.storch@neuro.med.tu-dresden.de
Insights
A new method using diluted blood and wet preparations accurately detects acanthocytosis, a key indicator for neuroacanthocytosis syndromes like chorea-acanthocytosis. This approach establishes normal acanthocyte values for diagnosing movement disorders.
Area of Science:
- Hematology
- Neurology
- Clinical Diagnostics
Background:
- Acanthocytosis in peripheral blood smears is crucial for diagnosing neuroacanthocytosis syndromes, including chorea-acanthocytosis (ChAc) and McLeod syndrome.
- Genetic testing is limited for most neuroacanthocytosis disorders, and standardized methods for quantifying acanthocytes are lacking.
Purpose of the Study:
- To establish reference values for acanthocytes in healthy volunteers and patients with movement disorders (MDs).
- To evaluate a novel method for acanthocyte detection using light microscopy, isotonic dilution, and wet preparations.
Main Methods:
- A prospective, reader-blinded study involving 100 patients with MDs, 31 with unclassified MDs, and 37 healthy controls.
- Erythrocyte morphology was assessed using light microscopy in standard EDTA and isotonically diluted blood samples, both as dry smears and unfixed wet preparations.
- Normal values were defined as the 99th percentile of combined results from healthy volunteers and patients.
Main Results:
- Isotonic dilution and wet preparations significantly increased acanthocyte detection compared to standard EDTA dry smears.
- No significant differences in acanthocyte levels were found between patients with diagnosed MDs and healthy volunteers across all conditions.
- The method using diluted blood and wet preparations demonstrated high specificity (0.98) and sensitivity, detecting all genetically confirmed ChAc patients.
Conclusions:
- A standardized method using isotonically diluted blood and unfixed wet preparations is recommended for detecting clinically relevant acanthocytosis in movement disorders.
- The recommended normal range for acanthocytes is <6.3% of total erythrocytes.
- This cost-effective and accessible method offers high diagnostic accuracy for movement disorders associated with acanthocytosis.
Abstract:
The presence of acanthocytosis in peripheral blood smears remains the hallmark of the clinical diagnosis of most neuroacanthocytosis syndromes, such as chorea-acanthocytosis (ChAc) and McLeod syndrome. Genetic analyses and/or specific laboratory tests are available only for a minority of these disorders. Testing for acanthocytosis is hampered by the lack of data on normal amounts of acanthocytes assessed by a standardized method. We report a prospective reader-blinded study designed to establish control values for abnormally shaped erythrocytes in healthy volunteers and patients with movement disorders (MDs) using light microscopic assessment of erythrocyte morphology in standard EDTA and isotonically diluted blood samples. We investigated a total of 100 patients fulfilling clinical criteria of specific MDs, 31 patients with MDs not matching any clinical criteria, and 37 healthy controls. In patients with diagnosed MDs and healthy controls, acanthocytes in dry blood smears were significantly more frequent following isotonic dilution compared with standard EDTA blood. In unfixed wet blood preparations of both EDTA blood and isotonically diluted blood, acanthocyte levels were significantly higher than in standard dry blood smear preparations. There were no statistical differences of acanthocyte levels in all test conditions between diagnosed MDs and healthy volunteers. There was no significant correlation of acanthocyte levels in all blood samples and preparations with age, sex or diagnosis. Thus, normal values were defined as the 99th percentile of combined results of the two groups of volunteers. Diluted blood combined with wet blood preparation showed high specificity (0.98) and the highest sensitivity of all test procedures (all genetically confirmed ChAc patients were detected). The reported method is cheap, readily available, and provides high specificity and sensitivity in respect to clinically relevant acanthocytosis. The use of isotonically diluted blood samples combined with unfixed wet blood preparation with a normal range of <6.3% of total erythrocytes is recommended to search for significant acanthocytosis in movement disorders.
