Velayos Baeza A., Dobson-Stone C., Rampoldi L., Bader B., Walker RH., Danek A., Monaco AP.
CLINICAL CHARACTERISTICS: Chorea-acanthocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavior changes, a myopathy that can be subclinical, and chronic hyperCKemia in serum. Although the disorder is named for acanthocytosis of the red blood cells, this feature is variable. The movement disorder is mostly limb chorea, but some individuals present with parkinsonism. Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and serious dysphagia with resultant weight loss. Habitual tongue and lip biting are characteristic, as well as tongue protrusion dystonia. 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 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 may lead to major disability within a few years. Life expectancy is reduced, with age of death ranging from 28 to 61 years. DIAGNOSIS/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-weighted 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 kinase (CK) is observed in the majority of affected individuals. Muscle biopsy reveals central nuclei and atrophic fibers. VPS13A, which encodes chorein, is the only gene in which mutation is currently known to cause ChAc. MANAGEMENT: Treatment of manifestations: Treatment is purely symptomatic, and may include: botulinum toxin for decreasing the oro-facio-lingual dystonia; feeding assistance; speech therapy; mechanical protective devices; splints for foot drop; phenytoin, clobazam, valproate, and levetiracetam for seizure management; antidepressant or antipsychotic medications; dopamine antagonists/depleters 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 assure adequate caloric intake and to prevent aspiration; EEG every third year. Agents/circumstances to avoid: Seizure-provoking circumstances and anticonvulsants that may worsen involuntary movements. 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. Carrier testing for at-risk relatives is possible if the pathogenic variants in the family are known. Prenatal testing is possible for families in which the pathogenic variants are known.