Chorea-acanthocytosis is a rare genetic disorder of the nervous system. It causes involuntary jerks and twitches in the muscles, known as chorea, and star-shaped red blood cells, known as acanthocytosis.

Chorea-acanthocytosis (ChAc) is a very rare, hereditary neurodegenerative disorder. The characteristic features of the condition are problems with movement and star-shaped red blood cells.

The condition occurs due to a genetic alteration that affects a protein known as chorein. The variation causes this protein to be much smaller and nonfunctional. However, researchers are currently unsure how this genetic change causes the symptoms of ChAc. At present, there is no cure for ChAc, but many treatment options are available to help relieve symptoms.

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ChAc is a type of neuroacanthocytosis. This term refers to a group of conditions that cause movement problems and star-shaped red blood cells. ChAc is a rare condition. Evidence suggests that only 500 to 1,000 people worldwide have the condition.

What is chorea?

Chorea refers to the specific type of jerking, twitching, or dance-like movements that occur in people with ChAc. Health experts define chorea as a state of spontaneous, exaggerated movements that:

  • do not have regular timing
  • are not repetitive in nature
  • happen randomly
  • usually start and finish abruptly

This condition is also known as VPS13A disease, named after the gene that causes it to develop. Chorea can range from mild to severe.

Mild chorea comes and goes, causing uncontrollable fidgeting with the hands and exaggerated gestures and facial expressions. Severe chorea can lead to continuous, violent, involuntary movements that significantly interfere with daily function.

What is acanthocytosis?

Acanthocytosis is a condition that causes the formation of star-shaped red blood cells. It occurs when the proteins and fatty substances that make up the outer layers of cells undergo changes. These changes usually develop in people with severe liver problems, malnutrition, and low activity in the thyroid glands.

Certain conditions, such as neuroacanthocytosis, can lead to these abnormal cells. The name comes from the spikes or points called acanthocytes that develop on the outside of the cells. This shape may affect how the cells work as well as their ability to pass through the smallest blood vessels.

ChAc develops due to changes in the VPS13A gene. This gene has links to the body’s ability to make a protein called chorein. Although this protein’s function is not clear, chorein proteins are unusually small and do not work correctly in people with ChAc.

ChAc passes from parents to children in an autosomal recessive pattern. This means that a copy of the VPS13A gene variation has to pass down from each parent. If a person only has one copy, they can still pass on the condition to their own offspring as a carrier. If they have a child with another carrier, the child may have the gene alteration and develop acanthocytosis.

Chorea is the main symptom of ChAc. This involves unwanted movements, usually affecting the arms and legs. These movements might include sporadic shoulder shrugs, pelvic thrusts, and a lurching walking style that includes involuntary knee flexing.

These symptoms often begin when a person is an adult and get worse over time. Other movement-based symptoms might include repeatedly dropping objects or repeatedly squeezing and releasing them while attempting a single gripping motion.

Dystonia is another common ChAc symptom. This involves involuntary muscle contraction and the contraction of certain body parts into atypical movements and postures. In those with ChAc, dystonia of the mouth and face are common.

Other common symptoms include:

  • nerve damage, leading to numbness and loss of reflexes
  • muscle wasting
  • weakness
  • seizures

Rarely, people with ChAc may develop symptoms that resemble those of Parkinson’s disease, including stiffness, tremors, and quiet speech.

Facial symptoms

When dystonia and chorea occur in the faces of people with ChAc, they can cause:

  • tongue thrusting
  • involuntary grimacing
  • unusual jaw movements
  • uncontrollable grinding of the teeth
  • excessive belching, spitting, or drooling
  • regularly biting the lips or tongue
  • swallowing difficulties
  • speech and communication difficulties
  • vocal tics including grunts and involuntary speech
  • slurred speech

Cognitive, personality, and behavioral symptoms

These may develop later on in the progression of ChAc. People with ChAc can experience:

  • apathy
  • depression
  • hyperactivity
  • irritability
  • slow thought processes
  • extreme mood changes
  • anxiety
  • aggression
  • paranoia
  • compulsive behaviors such as chronic hair-pulling

Complications

ChAc can eventually become so severe that some people with the condition develop the following complications:

  • a lost ability to walk independently, meaning they remain in bed or require a wheelchair
  • mutilation of the lips and tongue due to excessive involuntary biting
  • muteness or an inability to speak
  • dementia and progressive memory problems

A person with advanced ChAc may not be able to care for themselves.

There are no set diagnostic criteria for ChAc. Diagnosing ChAc involves ruling out conditions with similar symptoms, such as Huntington disease, and checking the blood for signs of acanthocytosis. This may involve:

  • a detailed medical examination to identify its main symptoms
  • blood tests, which often show high serum creatine kinase levels
  • genetic testing, which can show changes to the VPS13A gene
  • MRI and CT scans, which can show brain changes
  • electromyography (EMG), which can demonstrate muscle and nerve function and identify problems

Currently, there is no cure for ChAc. However, several treatments can help people manage individual symptoms, preserve function, and maintain quality of life.

Psychiatric symptom management and chorea treatment

Dopamine-receptor blocking drugs play a role in reducing chorea movements, as dopamine is crucial for brain functions including movement control.

People with ChAc might also benefit from using additional medications when symptoms arise, such as:

Seizure treatment

Almost half of all people with ChAc live with regular seizures and may need to take anticonvulsants such as phenytoin and valproate. However, some antiseizure medications may make chorea worse and might not be suitable for some people with ChAc.

Dystonia treatment

Botulinum toxin (Botox) injections may help people reduce or resolve muscle spasms due to dystonia. The effects may take 5 to 10 days, and people may need to have another injection every 3 to 4 months.

Nutritional support

As people with ChAc may have difficulty chewing and swallowing food, it is vital for people to monitor their nutritional status. They may need support from a dietitian or nutritionist. Individuals with ChAc may also need to supplement vitamins and minerals if they have low levels.

Doctors may insert feeding tubes for people with severe ChAc who can no longer eat.

Therapies to assist with daily function

Speech, physical, and occupational therapists may help preserve or restore a person with ChAc’s ability to move, speak, and work. Not every person will need these services, and a doctor will adjust their recommendations based on which symptoms interfere most with everyday function, as well as the stage of progression.

People may also benefit from using certain devices. A mouth guard can help limit damage to the tongue and lips from involuntary biting. Braces may support limb stability, and people may need a wheelchair to move around.

Computer-assisted speech devices can support communication in everyday life for people with ChAc.

Deep brain stimulation

People with ChAc might benefit from a surgical procedure called deep brain stimulation. A surgeon places an electrode in the brain and a small battery pack near the collarbone to control movements and block disruptive nerve signals that could have links to chorea and dystonia.

Genetic counseling

Genetic counseling may be beneficial for affected individuals and their families. It can help people with ChAc work out the risk of passing on the VPS13A gene and whether offspring might develop the condition.

Chorea-acanthocytosis is a rare type of neuroacanthocytosis. It causes brain and central nervous system symptoms as well as star-shaped red blood cells called acanthocytes. The main symptoms are chorea, which involves involuntary muscle movements, and dystonia, which leads to muscles staying contracted. Seizures and behavioral symptoms are also common.

The condition develops due to alterations in a gene called VPS13A. At present, there is no cure, and the disease can progress to a point where individuals can no longer eat, speak, or move unassisted. However, medications, devices, and various therapies can reduce the impact of chorea-acanthocytosis on everyday function.