What are other Names for this Condition? (Also known as/Synonyms)

• Acanthocytosis with Neurologic Disorder
• ChAc (Chorea-Acanthocytosis)
• Choreoacanthocytosis

What is Chorea-Acanthocytosis? (Definition/Background Information)

• Chorea-Acanthocytosis (ChAc) is an uncommon, genetic, and primarily neurological disorder. The disorder is caused by mutation(s) in the VPS13 gene (also known as the CHAC gene), which codes for a certain protein ‘chorein’. The exact function of this protein is unclear
• As the name of the disorder indicates, it is composed of 2 components - ‘chorea’ and ‘acanthocytosis’
  • Chorea is a neurological disorder that results in abnormal and repetitive movements of various parts of the body. These movements are uncontrolled and characterized by jerky actions
  • Acanthocytosis is a disorder of red blood cells resulting in abnormal shape of red cells. The red cells normally have a smooth outer surface. In acanthocytosis, the red cells have abnormal spikes in the outer surface, which affect their function
• Apart from movement problems, individuals with this disorder also have abnormal muscle tone called dystonia, in which the muscles of the face, hands, legs, tongue, and throat are affected
• Blood tests (including examination of blood under the microscope), imaging studies, and nerve biopsy are some methods that may be employed to diagnose the condition
• The condition is progressive and the treatment is generally geared toward supportive therapies to improve the quality of life of those affected
• In many cases, the prognosis is poor for individuals with Chorea-Acanthocytosis, due to shortened life expectancies. Also, since Chorea-Acanthocytosis is a genetic disorder, there are no preventive methods or guidelines currently available for this condition

Who gets Chorea-Acanthocytosis? (Age and Sex Distribution)

• Chorea-Acanthocytosis is a rare genetic disorder with less than 1000 cases reported worldwide. The exact prevalence of this disorder is not known
• However, some individuals of Japanese origin and certain French-Canadian families have elevated occurrence of ChAc
• The average age of symptom-onset is approximately 30 years, although manifestations of the disorder may begin as early as childhood or even as late as 70 years
• Both males and females may be affected by this genetic condition, although males appear to be more susceptible to the disorder than females

What are the Risk Factors for Chorea-Acanthocytosis? (Predisposing Factors)

• Chorea-Acanthocytosis is a genetic disorder, and therefore, having a family history of ChAc is a major risk factor for being diagnosed with the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chorea-Acanthocytosis? (Etiology)

Chorea-Acanthocytosis is caused by mutation(s) in the VPS13A gene (also known as the CHAC gene)

• Under normal circumstances, this gene codes for the ubiquitous protein “chorein”. The exact function of chorein is not known; but, it is believed that it is involved in intra-cellular protein transportation
• When VPS13A gene is mutated, the resultant product is truncated and therefore, non-functional
  • The abnormal chorein possibly leads to aberrant movement of proteins within the cells of the brain as well as involving the red blood cells, causing the characteristic symptoms observed with the disorder
  • Although, the chorein protein is distributed everywhere in the human body, the VPS13A mutation(s) seem to affect the brain and red blood cells exclusively. The exact reason for this specificity is not clear
• Chorea-Acanthocytosis is inherited in an autosomal recessive pattern. In this type of inheritance, an individual must inherit both copies of the causative gene in the defective form for the disorder to manifest itself. An affected individual inherits one defective copy of the gene from each parent, who themselves are carriers of ChAc, but typically remain unaffected

What are the Signs and Symptoms of Chorea-Acanthocytosis?

The signs and symptoms of Chorea-Acanthocytosis may manifest subtly in the early stages, and may progress steadily. The following are some characteristic features of ChAc:

• Abnormal red blood cells (acanthocytosis)
• Seizures particularly, temporal lobe epilepsy
• Speech impairment
• Difficulty in learning
• Frequent mood swings leading to behavioral issues. This may resemble frontal lobe syndrome in its signs and symptoms
• Difficulty in memory
• Involuntary jerking movements; difficulty in walking or running due to muscle wasting and weak muscles
• Sensory peripheral neuropathy - decreased sensation of extremities such as legs and arms
• Tense muscles, which are occasionally painful, dystonia of limbs, face, mouth, tongue, and throat
  • Involuntary twitching of tongue leading to accidental injury to tongue
  • Difficulty in chewing and swallowing food
  • Squint eyes
  • Frequent belching resulting in reflux disease
• Behavioral symptoms, such as obsessive-compulsive disorder (OCD), and inability to control emotions
• Splenomegaly or enlargement of spleen
• Hepatomegaly or enlargement of liver

How is Chorea-Acanthocytosis Diagnosed?

The diagnosis of Chorea-Acanthocytosis is made by the following tests and exams:

• A thorough physical examination and an assessment of symptoms
• Evaluation of family medical history
• Examination of peripheral red blood cells under a microscope by a pathologist
• Blood test to check for levels of the following in serum:
  • Creatine kinase
  • Lactate dehydrogenase (LDH)
  • Aminotransferase enzyme (AST)
  • Alanine aminotransferase (ALT)
• Muscle biopsy to check for atrophy of muscle fibers
• Peripheral nerve biopsy to check for atrophy of nerve fibers
• Western blot test to check for abnormality in chorein protein
• Electromyography to determine abnormalities in muscle tissue
• Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the brain
• Genetic molecular testing for the mutations in VPS13A gene, which may help confirm the initial diagnosis
• Prenatal genetic molecular testing, to detect gene mutation(s) in the unborn child

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chorea-Acanthocytosis?

The potential complications of Chorea-Acanthocytosis include:

• Fall injuries due to muscle weakness
• Damage to tongue during convulsions
• Progressive weakness, making daily activities more difficult
• Systemic infections
• Aspiration pneumonia, which can be fatal

How is Chorea-Acanthocytosis Treated?

There is no definitive treatment for curing Chorea-Acanthocytosis. The treatment is generally geared toward alleviating symptoms, and may include the following:

• Botulinum toxin for involuntary contractions involving the jaw and mouth
• Assistance with feeding, if needed
• Mouth guard to prevent damage to tongue
• Medication for convulsions
• Behavioral treatment according to symptoms noted
• Splints for foot drops
• Speech therapy
• Behavioral therapy and counseling

How can Chorea-Acanthocytosis be Prevented?

At the present time, there are no methods or guidelines available for the prevention of Chorea-Acanthocytosis, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in better understanding of the risks during pregnancy
• If there is a family history of the condition, then genetic counseling may help couples assess risks while planning for a child
• Active research to explore treatment and prevention options for inherited disorders such as Chorea-Acanthocytosis is currently being conducted
• Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended

What is the Prognosis of Chorea-Acanthocytosis? (Outcomes/Resolutions)

The prognosis of Chorea-Acanthocytosis is typically poor. It is a progressive disease and the symptoms worsen over time. This also makes it difficult in leading a normal life.

• With appropriate supportive care, the quality of health of the affected individual may be improved
• Seizures and aspiration pneumonia can lead to fatalities

Additional and Relevant Useful Information for Chorea-Acanthocytosis:

Please visit our Rare Diseases & Disorders Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/rare-disorders/