Chorea-Acanthocytosis
Chorea-acanthocytosis is a rare hereditary neurological disorder characterized by progressive involuntary movement problems, cognitive changes, and distinctly misshapen red blood cells.
Overview
Chorea-acanthocytosis is primarily a neurological condition that impairs movement across many parts of the body. It is classified as one of the neuroacanthocytoses, a group of disorders characterized by the combination of neurological abnormalities and star-shaped red blood cells known as acanthocytosis. Movement difficulties and other neurological issues typically begin during early to mid-adulthood and worsen over time due to cell loss (atrophy) in specific regions of the brain.
Symptoms
The clinical presentation of chorea-acanthocytosis includes a wide range of motor, systemic, cognitive, and behavioral signs:
Movement Problems
- Chorea: Involuntary, rapid, jerking movements affecting various body regions.
- Dystonia: Involuntary sustained muscle tensing, particularly involving the face, mouth, tongue, throat, and limbs.
- Spasms and Vocal Tics: Muscle twitches that trigger limb spasms, vocalizations such as grunting, and involuntary belching.
- Oral Complications: Twitches of the tongue and throat that interfere with chewing and swallowing, alongside uncontrolled, self-injurious biting of the tongue, lips, and inner mouth.
Additional Neurological and Muscular Features
- Seizures: Occurring in nearly half of all affected individuals.
- Peripheral Neuropathy: Reduced sensation and weakness in the arms and legs resulting from nerve dysfunction.
- Myopathy: Muscle weakness.
- Speech Difficulties: Progressive impairment in nerve and muscle function that affects speech and can eventually result in an inability to speak.
- Cognitive Impairment: Difficulty processing, learning, and recalling information.
Behavioral and Psychiatric Changes
Behavioral changes are common and may represent the earliest indicators of the condition. These include:
- Personality changes
- Obsessive-compulsive disorder (OCD)
- Lack of self-restraint
- Inability to manage self-care
Frequency
Chorea-acanthocytosis is an exceptionally rare disorder, with an estimated global prevalence of 500 to 1,000 individuals.
Causes & Genetics
The disorder is caused by mutations in the VPS13A gene. This gene provides instructions for synthesizing a protein named chorein. Although chorein is active (expressed) in cells throughout the body, its precise biological role is not yet fully understood, though researchers suspect it participates in the trafficking of proteins within cells.
Most mutations in VPS13A cause cells to generate an abnormally short, nonfunctional version of the chorein protein. It remains unclear why the absence of this widely expressed protein selectively damages only red blood cells and the central nervous system.
Inheritance
Chorea-acanthocytosis is inherited in an autosomal recessive pattern. This means an individual must inherit two altered copies of the VPS13A gene (one in each cell) to develop the condition. Parents of an affected individual typically carry one mutated gene copy and are asymptomatic, showing no features of the disorder.
Other Names
- CHAC
- Choreoacanthocytosis
- Neuroacanthocytosis