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Chorea-acanthocytosis
1
Department of Clinical
Neuroscience, Charing Cross
Hospital Campus, Imperial
College London, London, UK
2
Department of Neurology,
University of Luebeck, Luebeck,
Germany
Correspondence to
Dr Peter G Bain, Department of
Clinical Neuroscience, Charing
Cross Hospital Campus, Imperial
College London, Charing Cross
Hospital, Fulham Palace Road,
London W6 8RF, UK;
p.bain@imperial.ac.uk
Received 5 May 2011
Accepted 2 August 2011
40 Practical neurology 2012;12:40–43. doi:10.1136/practneurol-2011-000045
Elisaveta Sokolov,1 Susanne A Schneider,1,2 Peter G Bain1
Neuroacanthocytosis (NA) is typi-
fied by choreiform movements
and acanthocytes in the peripheral
blood. It comprises four genetically
diverse conditions, one of which is
chorea-acanthocytosis. The authors
describe a 38-year-old woman
who presented with facial grimac-
ing, dysphagia and acquired stutter.
Chorea-acanthocytosis was eventually
confirmed by the finding of bilateral
caudate atrophy on MRI brain scan,
acanthocytes in the peripheral blood
film, increased serum creatine kinase
and a low serum chorein level. The
authors discuss the clinical features,
differential diagnosis and management
of chorea-acanthocytosis.
Introduction
Neuroacanthocytosis (NA) is a rarely
reported syndrome affecting the nerv-
ous system, first described by Bassen
and Kornzweig in 1950.1 NA comprises
four genetically diverse conditions: the
two core conditions are chorea-acan-
thocytosis and the McLeod syndrome,
but acanthocytes also characterise two
other neurological conditions, pan-
tothenate kinase-associated neurode-
generation and Huntington’s disease
(HD)-like 2.2 3
We describe a case of chorea-acan-
thocytosis, an autosomal recessive dis-
order, estimated to affect about 1000
people worldwide, with a mean age of
symptom onset of around 35 years. It
manifests as a progressive movement
disorder that usually includes cho-
rea, seizures, behavioural and cogni-
tive disorders, peripheral neuropathy
and (often subclinical) myopathy.
Oral-lingual dystonia is a noticeable
feature, often resulting in mouth or
tongue lacerations. Prominent tongue
protrusion dystonia, sometimes
causing extrusion of food, is a useful
pointer towards the diagnosis.
Case report
A 38-year-old woman of Pakistani
descent presented in 2007, aged 34
years, with a 3-year history of facial
grimacing, dysphagia and acquired
stutter. The problem had started fol-
lowing the birth of her second child.
She complained of memory difficul-
ties, depressive symptoms, loss of
appetite, intermittent chest pain and
shortness of breath. She avoided din-
ing in public and had stopped working
as a catering assistant 1 year previously,
although she was able to perform her
activities of daily living.
When aged 2 years she had developed
‘fits’, during which she would stop
breathing with a staring expression.
Her seziures tended to be provoked by
stress and she would come out of them
quickly. The seziures resolved sponta-
neously by the age of 4 years.
There was no family history of
movement disorder; however, one
brother had epilepsy. Her parents
were first cousins, and there was also
consanguinity between other family
members. Her two children were well.
She was taking the contraceptive pill
Microgynon 30. She did not smoke
cigarettes or drink alcohol.
On examination, there were abnor-
mal facial movements, consistent with
tics, manifesting as eye twitching and
frequent blinking. She could suppress
these movements briefly. Occasionally
she would protrude her tongue. There
was mild dysarthria, a stammer and
she made intermittent clucking noises
in her throat. There was no obvious
movement disorder affecting her limbs
or trunk. The tone, power, coordina-
tion, reflexes and sensation in her

Figure 1 A normal spiral drawing at presentation, prior to the
development of limb chorea.
limbs were normal. Her gait was normal and
Romberg’s sign was negative. Her handwriting
and a drawing of a spiral were normal (figure 1).
Formal neuropsychological assessment was
unremarkable. Routine blood tests were normal,
including thyroid and liver function, plasma lip-
ids, serum caeruloplasmin, immunoglobulins,
rheumatoid factor, antinuclear antibody, antineu-
trophil cytoplasmic antibody, antistreptolysin-O
titre and antibasal ganglia antibodies. The serum
creatine kinase was slightly elevated. An initial
MRI scan of the brain was normal, except for
mild non-specific white matter changes; subse-
quent neuroimaging showed caudate atrophy.
Genetic testing for HD and dentatorubropallidol-
uysian atrophy was negative. The initial periph-
eral blood film for acanthocytes was negative.
However, further peripheral blood smears iden-
tified peripheral acanthocytes (figure 2). Protein
function tests showed reduced chorein levels, sug-
gesting chorea-acanthocytosis.
She stopped taking the contraceptive pill but
without noticeable benefit. Treatment trials with
baclofen and aripiprazole did not affect her
abnormal movements. Tetrabenazine exacerbated
her depressive symptoms and did not help the
movement disorder.
On review in 2011, when aged 38 years, she was
taking fluoxetine 20 mg daily, clonazepam 1 mg
at night and hyoscine 300 µg daily. She had mild
chorea in her limbs and unsteadiness when walk-
ing. Her dysarthria and dysphagia had become
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more marked and tongue protrusions resulted
in her pushing food from her mouth when eat-
ing. She coughed intermittently after swallowing
food and wore a ‘bite-guard’ on her upper and
lower teeth because of a marked tendency for her
mouth to shut and bite and lacerate her tongue.
She needed two hands to hold a cup and could
eat only with a fork or spoon in her left hand.
She had difficulty writing and tying buttons and
zips. A speech and language therapist had advised
her to drink thickened fluids to prevent escape of
food from her mouth.
On examination, there was marked dysarthria,
a tendency to make clucking and masticatory
sounds, excessive blinking, abnormal tic-like facial
movements, forcible dystonic mouth opening and
closure, and mild tongue protrusions. She had
mild chorea-tics affecting her limbs, especially on
the right side. The limb strength, reflexes and sen-
sation were normal. Her gait was normal but she
could not walk heel-to-toe.
Her serum creatine kinase was elevated at 1301
IU/l (24–170). A 12-lead ECG and echocardio-
gram were normal.
We administered botulinum toxin injections into
the masseter and temporalis muscles bilaterally to
very good effect, allowing her to dispense with
the ‘bite-guard’. The injections had no adverse
effects and she continues to receive them once
every 3 months.
Discussion
Chorea-acanthocytosis is a rare autosomal reces-
sive adult-onset neurodegenerative disorder
caused by mutations in the VPS13A gene, encod-
ing chorein, located on chromosome 9q21. It
manifests as a mixed movement disorder, typi-
cally including chorea, although there may also be
dystonia with prominent orofacial involvement,
tics and parkinsonism. Other features include sei-
zures, neuropathy, myopathy, autonomic features,
dementia and psychiatric features.
The differential diagnosis is wide because of the
protean manifestations of chorea-acanthocytosis.
Conditions to consider include the general cat-
egories of parkinsonian syndromes, choreiform
and other movement disorders, epilepsy disorders
and neuromuscular disorders. McLeod syndrome
is particularly important as it also shows an ele-
vated serum creatine kinase and acanthocytes in
the peripheral blood smear. McLeod syndrome is
caused by several recessively inherited mutations
in the XK gene on the X chromosome, a gene
responsible for producing a specific protein (Kell
Practical neurology 2012;12:40–43. doi:10.1136/practneurol-2011-000045 41
 NEUROLOGICAL RARITY
Figure 2 An electron micrograph of a peripheral blood film
demonstrating acanthocytes (arrowed). Image courtesy of the
National Institutes of Health Clinical Center and National Heart
Lung and Blood Institute (McDonald Horne, Kazuyo Takeda,
Zu-Xi Yu, Bill Riemenschneider and Adrian Danek).
antigen) on the red blood cell surface. Patients
with McLeod syndrome commonly have haemo-
lytic anaemia, cardiomyopathy and peripheral
neuropathy and may manifest chorea, facial tics as
well as lip and tongue biting. Wilson’s disease, HD
and the Huntington-like disorders must also be
excluded, although chorea-acanthocytosis, unlike
HD, is autosomal recessive and more frequently
associated with seizures. Chorea-acanthocytosis is
an important differential diagnosis in movement
disorder patients with known consanguinity in
the family (as in this case), as well as in sporadic
cases.
The MRI brain scan in chorea-acanthocytosis
shows progressive caudate atrophy with predi-
lection for the head of caudate, more marked
than in HD. In addition, T2-weighted MRI often
shows increased signal in the putamen and cau-
date nuclei. The peripheral blood smear shows
increased numbers (5–50%) of acanthocytes—
erythrocytes of approximately spherical shape
bearing 2–20 spicules of unequal length and dis-
tributed irregularly over the red blood cell surface
(figure 2)—characteristic of the neurocanthocyte
syndromes. However, as in this case, acanthocytes
are not always initially detected: multiple smears
using unfixed wet blood preparations of isotoni-
cally diluted blood should be obtained on three
independent occasions.
42 Practical neurology 2012;12:40–43. doi:10.1136/practneurol-2011-000045
Practice points
■ Chorea-acanthocytosis is a complex autosomal recessive
adult-onset neurodegenerative disorder. It often manifests
with a mixed movement disorder, in which chorea, tics,
dystonia and even parkinsonism may occur.
■ Orolingual dystonia, in particular prominent tongue
protrusion, can be a useful clinical clue towards the
diagnosis.
■ Chorea-acanthocytosis should be considered in patients with
elevated levels of acanthocytes in a peripheral blood film.
It is often necessary to sample blood on multiple occasions,
with a specific request to the haematologist to examine the
film for acanthocytes. The serum creatine kinase is often
elevated. Protein function tests demonstrating reduced
chorein levels and genetic analysis can confirm the diagnosis.
■ Treatment for chorea-acanthocytosis is symptomatic.
Botulinum toxin injections can help to control orolingual
dystonia.
■ Patients with chorea-acanthocytosis should undergo a
cardiac evaluation every 5 years to look for cardiomyopathy.
■ Prenatal testing may be available for families who have a
known disease-causing mutation.
The serum creatine kinase is generally elevated
in chorea-acanthocytosis. A protein assay show-
ing a reduced level of chorein (as in this case) and
genetic testing may be useful to confirm the diag-
nosis. Genetic testing, however, is labour inten-
sive due to the large size of the gene, containing
73 exons.
Autopsy studies have shown atrophy of the cau-
date nucleus but well preserved cerebral cortex.
Histological examination may show severe neu-
ronal loss and moderate astrocytic gliosis in the
caudate and putamen, with similar but less marked
findings in the pallidus and substantia nigra. The
small striatal neurons may be more severely depop-
ulated than the large neurons. Peripheral nerve
biopsies have shown axonal changes with depletion
of large myelinated fibres and myopathic changes
have also been described on muscle biopsy.
The treatment of chorea-acanthocytosis is symp-
tomatic. Neuroleptics can alleviate chorea but
may induce parkinsonism; dopamine depleting
drugs such as tetrabenazine may cause or exacer-
bate depression. Botulinum toxin injections may
help control orofacial–bucco-lingual dystonia,
preventing damage to the tongue and mouth,
facilitating eating and drinking and decreasing
bruxism. Mechanical protective devices may help
to prevent self-injury to the tongue and mouth.
Bilateral deep brain stimulation of either the ven-
tralis intermedius nucleus of the thalamus or the
globus pallidus internus has occasionally been

deployed, with variable outcomes. Some patients
need treatment to control seizures, mood dis-
turbances and other psychiatric features; many
need careful monitoring of nutritional status and
regular review by a speech therapist, as well as
physiotherapy and occupational therapy. Patients
should undergo cardiac evaluations every 5 years
to look for cardiomyopathy. Genetic counsel-
ling by a multidisciplinary team is recommended
and prenatal testing may be available for families
known to have a disease-causing mutation.
Acknowledgements The authors thank Dr Benedikt Bader
and Professor Adrian Danek, University of Munich, for
figure 2 and Professor Barbara Bain, Imperial College
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London for information on acanthocytes. This paper
was reviewed by Richard Hardie, Bristol, UK.
Competing interests None.
Provenance and peer review Commissioned;
externally peer reviewed.
References
1. Bassen FA, Kornzweig AI. Malformation of the erythrocytes in
a case of atypical retinitis pigmentosa. Blood 1950;5:381–7.
2. Danek A, Walker RH. Neuroacanthocytosis. Curr Opin Neurol
2005;18:386–92.
3. Schneider SA, Walker RH, Bhatia KP. The Huntington’s
disease-like syndromes: what to consider in patients with a
negative Huntington’s disease gene test. Nat Clin Pract Neurol
2007;3:517–25.
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