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Chorea-acanthocytosis
This rare condition primarily affects the brain and nervous system, leading to a range of neurological symptoms. It is caused by genetic changes and typically becomes apparent in adulthood, progressing gradually over time.
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Overview
Chorea-acanthocytosis is a very rare, inherited neurological condition that primarily affects the brain and nerve cells. It is one of a group of disorders known as neuroacanthocytosis syndromes, which share features of neurological dysfunction and abnormal red blood cell shapes [PMID:33671239]. The term 'chorea' refers to uncontrolled, jerky movements, while 'acanthocytosis' describes the presence of spiky or 'thorny' red blood cells, which are visible under a microscope.
This condition typically begins in adulthood, most often between the ages of 20 and 40, though onset can vary [PMID:20301389]. Symptoms usually worsen over time, impacting movement, cognitive function, and mental health. Due to its rarity and variable presentation, diagnosis can sometimes be challenging.
Symptoms & clinical features
The symptoms of chorea-acanthocytosis are diverse and affect multiple body systems, predominantly the neurological system. Involuntary movements are a hallmark feature, including chorea (brief, irregular movements), dystonia (sustained muscle contractions causing twisting or repetitive motions), and tics (sudden, repetitive movements or sounds) [PMID:20301389]. Difficulties with speech and swallowing (dysarthria and dysphagia) are also common.
In addition to motor symptoms, individuals may experience cognitive and psychiatric symptoms. These can include memory problems, difficulty with executive functions (planning, problem-solving), personality changes, depression, and obsessive-compulsive behaviours. Muscle weakness and wasting can also occur. The red blood cell abnormality (acanthocytosis) usually does not cause anaemia or other blood-related issues directly, but it is an important diagnostic marker [PMID:20301389].
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Affected organs
Chorea-acanthocytosis primarily affects the brain, particularly areas involved in controlling movement, such as the basal ganglia. Damage to nerve cells in these regions leads to the characteristic motor symptoms. Peripheral nerves, which transmit signals between the brain and the rest of the body, can also be affected, leading to muscle weakness and wasting.
The condition also impacts red blood cells, causing them to develop an unusual, spiky shape. While this abnormality is crucial for diagnosis, it typically does not lead to significant health problems related to blood function itself. Other organs can be indirectly affected by the progressive neurological decline, impacting overall physical health.
Risks & severity
Chorea-acanthocytosis is a progressive disorder, meaning symptoms generally worsen over time. The severity and rate of progression can vary significantly among affected individuals. As the disease advances, symptoms such as difficulty swallowing can lead to serious complications, including aspiration pneumonia.
The age of onset is typically between 20 and 40 years, though a wider range has been observed. Lifelong care and management are usually required. Exact prevalence is not well established due to the condition's rarity, but it is considered one of the rarest neurological disorders.
Genetic causes
Chorea-acanthocytosis is caused by pathogenic variants in the VPS13A gene. This gene provides instructions for making a protein called vacuolar protein sorting 13 homolog A, or chorein. Chorein is found in many cell types throughout the body, including brain cells and red blood cells.
The precise function of chorein is still an area of active research, but it is thought to play a role in transporting lipids (fats) and possibly other molecules between different compartments within cells. Pathogenic variants in VPS13A lead to a deficiency or absence of functional chorein, which is believed to disrupt normal cellular processes, particularly in nerve cells and red blood cells [PMID:33671239]. This cellular dysfunction underlies the neurological decline and the characteristic red blood cell changes observed in chorea-acanthocytosis.
- VPS13A vacuolar protein sorting 13 homolog A
Inheritance pattern
Chorea-acanthocytosis is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic variant in the VPS13A gene - one from each parent - to develop the condition. If a person inherits only one copy of the pathogenic variant, they are a carrier and typically do not show symptoms of the disorder.
Parents who are both carriers have a 1 in 4 (25%) chance with each pregnancy of having a child affected by chorea-acanthocytosis. They also have a 2 in 4 (50%) chance of having a child who is a carrier, and a 1 in 4 (25%) chance of having a child who inherits two normal copies of the gene and is neither affected nor a carrier. Genetic counselling can provide detailed information and support for families regarding inheritance patterns and risks.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosing chorea-acanthocytosis typically involves a combination of clinical evaluation, neurological assessment, and laboratory tests. The presence of characteristic neurological symptoms, particularly chorea and dystonia, along with psychiatric features, often prompts suspicion.
Confirmation of diagnosis usually relies on genetic testing for pathogenic variants in the VPS13A gene. Blood tests can also identify acanthocytes (spiky red blood cells) on a peripheral blood smear, which is highly suggestive of the condition, though not all affected individuals will have a high percentage of these cells [PMID:20301389]. In the UK, genetic testing for suspected inherited neurological disorders is part of the NHS Genomic Medicine Service pathway. Referrals for genetic testing are typically made by neurologists or clinical geneticists, under relevant R-codes for neurodegenerative disorders, such as R337 Neurodegenerative disorders with an adult onset.
Management & lifestyle
Currently, there is no cure for chorea-acanthocytosis; however, management focuses on alleviating symptoms and improving quality of life. Treatment is multidisciplinary and tailored to the individual's specific symptoms. Medications may be used to help control movement disorders like chorea and dystonia, and to manage psychiatric symptoms such as depression or obsessive-compulsive behaviours.
Physical, occupational, and speech therapy are often beneficial to maintain mobility, assist with daily activities, and improve communication and swallowing difficulties. Nutritional support is important, especially if swallowing becomes severely impaired. Regular follow-up appointments with neurologists and other specialists are crucial. Clinical geneticists and genetic counsellors can provide valuable support for patients and their families, discussing the condition, inheritance, and family planning options within the NHS framework.
UK care pathway
In the UK, individuals suspected of having rare genetic conditions like chorea-acanthocytosis are typically referred through general practitioners or specialist clinics to the NHS Genomic Medicine Service. This pathway enables access to specialist genetic clinics and testing. Clinical geneticists, neurologists, and specialist genetic counsellors work together to provide comprehensive care. Genetic testing is available for neurodegenerative disorders under specific R-codes, ensuring a standardised approach to diagnosis and ongoing management support.
Frequently asked questions
What causes chorea-acanthocytosis?
Chorea-acanthocytosis is caused by inheriting two pathogenic copies of the VPS13A gene, one from each parent. These genetic changes lead to a deficiency of the chorein protein, which is important for normal cell function, particularly in the brain and red blood cells.
Is chorea-acanthocytosis inherited?
Yes, it is inherited in an autosomal recessive pattern. This means both parents must be carriers of a pathogenic variant in the VPS13A gene for their child to be at risk of inheriting the condition. Carriers typically do not experience symptoms.
When do symptoms of chorea-acanthocytosis usually appear?
Symptoms of chorea-acanthocytosis most commonly begin in adulthood, typically between the ages of 20 and 40. However, the age of onset can vary among individuals, and symptoms may progress gradually over time.
Can chorea-acanthocytosis be cured?
Currently, there is no cure for chorea-acanthocytosis. Treatment focuses on managing the symptoms to improve the individual's quality of life. This can involve medications to control movements and psychological symptoms, as well as various forms of therapy.
How is chorea-acanthocytosis diagnosed in the UK?
Diagnosis in the UK typically involves a neurological assessment, identification of characteristic symptoms, and often a blood test to look for abnormal red blood cells (acanthocytes). The diagnosis is confirmed through genetic testing for pathogenic variants in the VPS13A gene via the NHS Genomic Medicine Service pathway.
References
- Adam MP, Bick S, Mirzaa GM. VPS13A Disease. 1993. PMID: 20301561
- Feriante J, Gupta V. Neuroacanthocytosis. 2023. PMID: 32809602
- Walker RH, Jung HH, Danek A. Neuroacanthocytosis. Handbook of clinical neurology. 2011. PMID: 21496574
- Nishizawa Y, Sakimoto H, Nagata O. Chorein deficiency promotes ferroptosis. FEBS open bio. 2025. PMID: 39514409
- Kumar N, Leonzino M, Hancock-Cerutti W. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. The Journal of cell biology. 2018. PMID: 30093493
- Rashid S, Malek N, Krommyda M. Chorea-acanthocytosis. Practical neurology. 2024. PMID: 38290845
- Danek A, Walker RH. Neuroacanthocytosis. Current opinion in neurology. 2005. PMID: 16003113
- Jung HH, Danek A, Walker RH. Neuroacanthocytosis syndromes. Orphanet journal of rare diseases. 2011. PMID: 22027213