Disease characteristics Chorea-acanthocytosis (ChAc) is characterized by a progressive movement
disorder, a myopathy that can be subclinical, cognitive and behavior
changes, and acanthocytosis of the red blood cells. The movement
disorder is mostly limb chorea, but some individuals present with a
parkinsonian syndrome. Dystonia is common and affects the oral region
and the tongue in particular, causing dysarthria and serious dysphagia
with resultant weight loss. Habitual tongue and lip biting are
characteristic. Progressive cognitive and behavioral changes resemble
those in a frontal lobe syndrome. Seizures are observed in almost half
of affected individuals and can be the initial manifestation. Myopathy
results in progressive distal muscle wasting and weakness. Mean age of
onset in ChAc is about age 35 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 may lead to major disability within a few years.
Life expectancy is reduced, with age of death ranging from 28 to 61
years. Diagnosis and testing 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. MRI
commonly shows T2-signal increase in the caudate and putamen.
Acanthocytes are present in 5%-50% of the red cell population. In some
cases, acanthocytosis may be absent or may appear only late in the
course of the disease. Increased serum concentration of muscle creatine
phosphokinase is observed in the majority of affected individuals.
Muscle biopsy reveals central nuclei and atrophic fibers. VPS13A,
encoding chorein, is the only gene currently known to be associated
with ChAc. Chorein detection
are available free of charge on a research basis only (see documents for sampling information). VPS13A molecular genetic testing is available at a commercial basis from the MGZ, Munich, Germany. Management Treatment of ChAc may include: botulinum toxin for decreasing the
oro-facio-bucco-lingual dystonia; feeding assistance; speech therapy;
mechanical protective devices; splints for foot drop; phenytoin,
clobazam, and valproate for seizure management; antidepressant or
antipsychotic medications; dopamine antagonists such as atypical
neuroleptics or tetrabenazine; and standard treatment for
cardiomyopathy. Surveillance includes monitoring of nutritional status
and adaptation of diet to assure adequate caloric intake, cardiac
evaluations every five years, and EEG every third year. | | Genetic counseling ChAc is inherited in an autosomal recessive manner. At conception, each
sib 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 a carrier. Prenatal testing may be available through
laboratories offering custom prenatal testing for families in which the
disease-causing mutations have been identified in an affected family
member. |