They are red blood cells whose shape resembles that of acanthus leaves.
This Mediterranean plant is characterized by the significant size of its leaves. Endowed with multiple spicules and surface projections, these red blood cells constitute an abnormality that is generally associated with lipids that have abnormal metabolism .
Acanthocytes are formed when free fatty acids bind in significant amounts to the red cell membrane of red blood cells.
Acanthocytes are found in the blood of individuals with ChAc in a highly variable proportion, generally 5% to 50% of the red blood cell population.
In some cases, acantocytosis may be absent or it may appear only late in the course of the disease.
The proportion of acantocytes does not correlate with the severity of the disease.
Scanning electron microscopy of glutaraldehyde-fixed erythrocytes is probably the most reliable method for detecting acanthocytes, but it is not routinely available.
A general standard for the determination of acantocytosis has been proposed.
Blood is diluted 1: 1 with 0.9% saline and 10 U / ml heparin, and examined using phase contrast microscopy after 30 minutes of incubation on a shaker.
In normal samples, less than 6.3% of the cells are spiculated [Storch et al 2005]. (Dried blood smears are often inappropriate.)
Acanthocytosis occurs due to ultrastructural abnormalities of the membranous skeleton of erythrocytes that result in a reduction in membrane fluidity.
At least three inherited neurological conditions are associated with it, although the pathogenesis of the neurological features is still unknown.
In abetalipoproteinemia, an autosomal recessive condition, vitamin E deficiency produces a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa.
Neuroacanthocytosis is also likely an autosomal recessive condition and is characterized by chorea, oro-faciolingual dyskinesia, dysarthria, areflexia, seizures, and dementia.
Detection of chorea-acanthocytosis (ChAc)
Western blot analysis revealed the absence or marked reduction of choreoin, the protein encoded by VPS13A, in erythrocytes from individuals with ChAc.
In contrast, normal levels of choreoin were observed in samples from individuals with McLeod syndrome and Huntington’s disease, suggesting that complete loss of choreain is a diagnosis of ChAc [Dobson-Stone et al 2004].
It is noteworthy that normal levels of choreoin are theoretically possible for some pathogenic variant alleles of VPS13A (eg, some error substitutions); therefore, the presence of normal levels of choreoin does not exclude the diagnosis of ChAc.
Chorea-acantocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavioral changes, a myopathy that may be subclinical, and chronic serum hyperCchemia.
Although the disorder is called red blood cell acantocytosis, this feature is variable. The movement disorder is mainly chorea of the extremities, but some people have parkinsonism.
Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and severe dysphagia with consequent weight loss. The usual features of tongue and lip biting are characteristic as well as tongue protrusion dystonia.
The progressive cognitive and behavioral changes resemble those of a frontal lobe syndrome. Seizures are seen in nearly half of affected individuals and may be the initial manifestation. Myopathy produces progressive distal muscle wasting and weakness.
The mean age of onset in ChAc is approximately 30 years, although ChAc can develop as early as the first decade or as late as the seventh decade.
It runs a chronic progressive course and can lead to significant disability within a few years. Life expectancy is reduced, with an age of death ranging between 28 and 61 years.
Diagnosis / test
The diagnosis of ChAc is based primarily on clinical findings, the presence of characteristic MRI findings, and evidence of muscle disease. CT and MRI reveal atrophy of the caudate nuclei with dilatation of the anterior horns of the lateral ventricles.
Magnetic resonance imaging commonly shows increased T2-weighted signal in the caudate and putamen. Acanthocytes are present in 5% -50% of the red blood cell population.
In some cases, acantocytosis may be absent or it may appear only late in the course of the disease. An increase in the serum concentration of muscle creatine kinase (CK) is observed in most affected individuals.
Muscle biopsy reveals central nuclei and atrophic fibers. VPS13A, which encodes for corein, is the only gene in which the mutation is currently known to cause ChAc.
Treatment of manifestations:
Treatment is purely symptomatic and may include:
- Botulinum toxin to decrease orofacio-lingual dystonia.
- Feeding assistance.
- Speech therapy.
- Mechanical protection devices.
- Splints for foot drop.
- Phenytoin , clobazam , valproate, and levetiracetam for the management of seizures.
- Antidepressant or antipsychotic medications.
- Dopamine antagonists / depletors such as atypical neuroleptics or tetrabenazine.
Deep brain stimulation may be helpful in selected cases.
- Surveillance : monitoring of nutritional status and adaptation of diet to ensure adequate caloric intake and avoid aspiration; EEG every third year.
- Agents / Circumstances to Avoid : Circumstances that cause seizures and anticonvulsants that can worsen involuntary movements.
ChAc is inherited in an autosomal recessive manner. At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not being a carrier.
Carrier testing for relatives at risk is possible if the pathogenic variants in the family are known. Prenatal testing is possible for families in which the pathogenic variants are known.