Second edition

08.qxd 3/10/08 9:38 AM Page 358
358 Neurodegenerative and movement disorders
picture and to unaffected relatives. Extensive counselling
resources should be available for instances when the test is
positive.
8.11 CHOREOACANTHOCYTOSIS
Choreoacanthocytosis, also known as chorea-acanthocytosis,
is a rare autosomal recessively inherited disorder
that typically manifests with chorea, as well as dementia in
roughly half of cases; in all cases one also finds an excessive
percentage of acanthocytic red blood cells. This last
characteristic, namely acanthocytosis, qualifies choreoacanthocytosis
as one member of a larger group of disorders
known as the neuroacanthocytoses, which, as noted
below in the discussion on differential diagnosis, includes
such conditions as the McLeod syndrome.
Clinical features
The onset is generally in the late twenties or early thirties
but may occur anywhere from late childhood to the seventh
decade. Clinically (Critchley et al. 1968; Feinberg et al.
1991; Hardie et al. 1991; Kartsounis and Hardie 1996;
Lossos et al. 2005; Sakai et al. 1981), most cases present with
a gradually progressive chorea, which, over time, is often
joined by other abnormal movements, such as tics, dystonia,
or a mild parkinsonism. A classic symptom, seen, however,
in only a minority, is self-mutilating lip- or tongue-biting.
Importantly, this self-mutilation is outside the patient’s
control: one patient (Medalia et al. 1989), despite attempting
to ‘restrain herself . . . by placing her fingers or a folded
towel in her mouth . . . nevertheless had bleeding and
scarred lesions of her oral mucosa and lips’. Most patients
will also develop a sensorimotor peripheral poly-neuropathy,
and, in a minority, seizures may occur. Roughly half of
all patients will also develop a personality change, a
dementia, or both.
Acanthocytosis to a degree of 10 percent or more is seen
on peripheral smears; importantly, the smears must be
fresh wet preparations and, given the chance of false
negatives, at least three smears should be examined
(Hardie et al. 1991). Genetic testing is available.
Creatinine kinase is elevated in most cases and MR
scanning may reveal atrophy of the caudate nucleus.
Course
The disease is gradually progressive, with death, on average,
after 14 years.
Etiology
Choreoacanthocytosis is an autosomal recessive condition
occurring secondary to mutations in the VPS13A gene on
chromosome 9q21 (formerly known as CHAC), which
codes for a protein known as chorein. There may be considerable
phenotypic heterogeneity in the same family.
Macroscopically, there is atrophy of the caudate, putamen,
and, to a lesser degree, the globus pallidus. Microscopically,
neuronal loss and gliosis are seen in these
structure and in the substantia nigra (Rinne et al. 1994b).
Axonal loss occurs in the peripheral nerves (Hardie et al.
1991; Ohnishi et al. 1981).
Differential diagnosis
The differential for chorea is discussed in Section 3.4; of
the disorders considered there, several others, in addition
to choreoacanthocytosis, present with chorea in early
adult years and must be distinguished from choreoacanthocytosis.
Huntington’s disease is marked by autosomal
dominant inheritance and an absence of a peripheral
neuropathy and, critically, a lack of acanthocytosis. As noted
earlier, other disorders, in addition to choreoacanthocytosis,
may also present with chorea and acanthocytosis, and these
include the McLeod syndrome and Huntington’s diseaselike
2 (Walker et al. 2002). The McLeod syndrome is distinguished
by X-linked inheritance and Huntington’s
disease-like 2 by an autosomal dominant pattern of inheritance.
Genetic testing is available for all of these disorders.
Treatment
As for Huntington’s disease, chorea may be treated with
antipsychotics; the general treatment of dementia is discussed
in Section 5.1.
8.12 FXTAS
FXTAS, also known as the fragile X-associated tremor/ataxia
syndrome, is a recently described inherited disorder characterized
by the gradual development of tremor, ataxia, and, in
a minority, dementia in middle-aged or older adults. This is
not an uncommon disorder, and although cases have been
reported in women (Hagerman et al. 2004), it is far more
common in men.
Clinical features
Clinical features have been described in a number of
papers (Greco et al. 2006; Hagerman et al. 2001; Hall et al.
2005). Although the age of onset ranges from the fourth to
the ninth decade, most patients fall ill in the seventh
decade with the gradual onset of ataxia and tremor. The
tremor, although typically of the intention type, may also
have a rest or postural component. Over time, a mild
parkinsonism may also accrue, with rest tremor, rigidity,