Levine–Critchley syndrome is an old name for a rare brain and blood disease that doctors now usually call chorea-acanthocytosis or VPS13A disease. It is a lifelong (chronic) genetic disease. It affects the deep parts of the brain that control movement, thinking, and mood (the basal ganglia), and it also changes the shape of some red blood cells into spiky cells called acanthocytes.
Levine-Critchley syndrome is an old name for a very rare inherited brain and blood disorder that doctors now usually call chorea-acanthocytosis or VPS13A disease, part of the “neuroacanthocytosis syndromes.” In this disease, deep parts of the brain that control movement (basal ganglia) slowly degenerate, and some red blood cells become spiky (“acanthocytes”). People may have jerky movements (chorea), mouth and tongue biting, swallowing problems, behavior changes, mood problems, seizures, and progressive disability. There is no cure yet, so treatment focuses on controlling symptoms, preventing complications, and supporting quality of life over many years.
Levine-Critchley syndrome is another name for chorea-acanthocytosis, a very rare inherited brain disease in the “neuroacanthocytosis” group.[1] It is caused by a change (mutation) in a gene that affects brain cells and red blood cells, so some red blood cells look spiky under the microscope (acanthocytes).[1] People usually develop symptoms in early or middle adult life. Common problems are jerky movements (chorea), mouth and tongue biting, trouble speaking, trouble swallowing, seizures, behavior and mood changes, weakness, and walking difficulty.[1] There is no cure yet, so treatment focuses on symptoms, safety, and quality of life.[2] Families often need long-term medical, psychological, and social support.[3]
In this disease, people slowly develop abnormal movements (especially in the face and mouth), trouble speaking and swallowing, changes in behavior and mood, seizures (fits), weakness, and loss of feeling in the hands and feet. Over many years, the brain cells in certain areas die (neurodegeneration), so symptoms usually get worse with time.
Levine–Critchley syndrome belongs to a small group of disorders called neuroacanthocytosis syndromes. In all of these, there are spiky red blood cells in the blood and damage in movement-control parts of the brain. The core diseases in this group are chorea-acanthocytosis and McLeod syndrome. Levine–Critchley syndrome is now understood to be the same as chorea-acanthocytosis in most families that were first described.
Most people with this condition have changes (mutations) in both copies of a gene called VPS13A. This gene gives instructions to make a protein called chorein, which seems to help cells handle fats and membranes. When chorein is missing or not working, nerve cells and red blood cells become unhealthy and start to fail.
The condition is very rare. Only a few hundred to about a thousand people are thought to have it worldwide. It affects males and females and usually starts in early or middle adult life (often around 25–40 years), but symptoms can sometimes begin earlier or later.
Other Names and Types
Doctors and researchers have used several names for this disease over time. These names can be confusing, but they are often describing the same or very closely related conditions.
Other names
Levine–Critchley syndrome
Chorea-acanthocytosis (ChAc)
Choreoacanthocytosis
VPS13A disease
Acanthocytosis with neurologic disorder
Neuroacanthocytosis (used more broadly for the whole group)
Today, experts prefer the name VPS13A disease (or chorea-acanthocytosis) because it points to the exact gene that is affected and avoids some confusion from older terms like Levine–Critchley syndrome, which are now considered historical or obsolete.
Types by clinical pattern (not official subtypes)
Doctors sometimes describe different patterns of Levine–Critchley / chorea-acanthocytosis instead of strict types, because the same disease gene can cause different dominant problems in different people or families:
Movement-dominant type – mainly abnormal movements (chorea, tics, dystonia, tongue and lip biting).
Epilepsy-dominant type – seizures are the first and main symptom for many years.
Psychiatric-dominant type – behavior change, mood problems, or obsessive-compulsive features come early.
Neuropathy-dominant type – numbness, weakness in limbs, and loss of reflexes are very clear.
Mixed type – combination of several features (movement, seizures, psychiatric, cognitive) from the start.
These “types” are just ways to describe how the disease shows itself in real people; they are not separate diseases.
Causes
Levine–Critchley syndrome has one main root cause: harmful changes in both copies of the VPS13A gene. The 20 points below break this main cause into simple pieces and related mechanisms to help understanding.
VPS13A gene mutation (core cause)
The direct cause is a mutation in the VPS13A gene. This mutation changes the “spelling” of the gene so the body cannot make normal chorein protein.Loss of chorein protein
Because of the gene mutation, chorein protein is missing or severely reduced. Without chorein, many cells, especially nerve cells and red blood cells, cannot handle their membrane and fat transport properly.Autosomal recessive inheritance
The disease usually follows an autosomal recessive pattern. This means a person must receive one faulty VPS13A gene from each parent to get the disease. Carriers with only one faulty copy usually have no symptoms.Parents who are carriers
When both parents silently carry one faulty VPS13A gene, each child has a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of having no faulty copy.Consanguinity (parents related by blood)
In some families, the parents are cousins or otherwise related. This increases the chance that they both carry the same rare VPS13A mutation and can pass two copies to a child.Frameshift or nonsense mutations
Some VPS13A mutations cut the gene early (nonsense or frameshift), making a very short, non-working protein or no protein at all. This usually leads to complete loss of chorein.Missense mutations (changed amino acids)
Other mutations change single building blocks of chorein (missense). These may make the protein unstable or unable to do its job, which still leads to disease.Large deletions or insertions in VPS13A
Some patients have bigger pieces of the VPS13A gene missing or extra. These structural changes prevent normal protein production and cause the disease.Basal ganglia degeneration
Loss of chorein over time leads to damage and shrinkage (atrophy) of the basal ganglia, especially the caudate nucleus and putamen. Damage in these areas is a direct biological reason for abnormal movements and cognitive problems.Abnormal red blood cell membranes
The same gene problem also affects red blood cell membranes, making some cells spiky (acanthocytes). This blood change is a sign of the disease and reflects the underlying membrane problem.Peripheral nerve damage (neuropathy)
Long-term chorein loss also harms peripheral nerves. This leads to reduced reflexes and numbness. It is part of the disease process, not a separate cause, but it explains many symptoms.Muscle involvement and high creatine kinase
Muscle fibers can be damaged, causing weakness and raised blood levels of creatine kinase (a muscle enzyme). This myopathy is linked to the same genetic problem.Progressive neuronal loss (neurodegeneration)
With time, many nerve cells in movement and thinking areas die and are not replaced. This gradual cell loss is a main reason symptoms get worse.Possible oxidative and cellular stress
Like other neurodegenerative diseases, stressed cell pathways (such as oxidative stress and abnormal cell clearance) are thought to play a role, although exact details in VPS13A disease are still being studied.Modifier genes and background genetic factors
Some people with the same VPS13A mutation have milder or more severe symptoms than others, suggesting that other genes in the body may modify the disease course.Possible environmental influences
There is no clear environmental “cause”, but general health, infections, or head injuries may influence when symptoms first appear or how fast they progress. This is based on general principles of brain disease rather than specific proof.Rare autosomal dominant families
A few older reports describe families with chorea-acanthocytosis-like illness and apparent autosomal dominant inheritance. These may represent different mutations or overlapping conditions. They show that genetic background can be complex.Misclassification with other neuroacanthocytosis syndromes
In the past, some families called “Levine–Critchley” had conditions that are now separated as McLeod syndrome or other neuroacanthocytosis diseases. This historical mix-up is a cause of name confusion, not a cause of the disease itself.Founder effects in certain populations
In some regions or families, a specific VPS13A mutation is shared by many related individuals (founder mutation). This local genetic history can increase the number of cases in that area.Unknown factors
Even with VPS13A mutations, doctors cannot always explain why one person gets seizures first and another gets movement problems first. This shows that there are still unknown factors that affect how the disease appears.
Symptoms
Not every person has all symptoms, but the following 15 features are common or important.
Chorea (dance-like movements)
Many people have fast, jerky, dance-like movements in the arms, legs, face, and trunk. These movements are not under the person’s control and may worsen with stress.Orofacial dyskinesia and self-biting
Involuntary movements of the tongue, lips, and face are very typical. People may bite their tongue or cheeks again and again, causing painful sores, and may stick out the tongue when trying to swallow.Feeding dystonia and swallowing difficulty
Some patients have “feeding dystonia,” where the jaw and tongue move in the wrong way when eating. This leads to choking, coughing, and taking a long time to finish meals.Speech problems (dysarthria)
Because the lips, tongue, and jaw move abnormally, speech becomes slurred, slow, or hard to understand. Over time, speaking may become very difficult.Seizures (epileptic fits)
Many people develop epileptic seizures. In some patients, seizures are the first or main symptom for years, which can cause confusion with other epilepsy syndromes.Psychiatric symptoms (mood and behavior changes)
Depression, anxiety, irritability, obsessive-compulsive behavior, or even psychosis (loss of contact with reality) can appear. Sometimes these changes start before movement problems.Cognitive decline (thinking problems)
Memory, planning, attention, and problem-solving can slowly worsen. This change often looks similar to Huntington disease and is sometimes called a “Huntington-like” picture.Peripheral neuropathy (numbness and weak reflexes)
Many patients have reduced or absent tendon reflexes and symptoms of neuropathy such as numbness, tingling, and weakness in the hands and feet.Muscle weakness and wasting (myopathy)
Damage to muscles and nerves can lead to thinning and weakness of limb muscles. Blood tests often show high creatine kinase, a sign of muscle breakdown.Walking and balance problems
Because of abnormal movements, weakness, and brain damage, people may have an unsteady gait, falls, and difficulty with fine motor tasks like using buttons or writing.Parkinsonism (slowness and stiffness)
In later stages, some individuals develop features like those of Parkinson disease: slowed movement, stiffness, and reduced facial expression, mixing with the chorea.Tics and other abnormal movements
Sudden, repetitive actions (tics), trunk spasms, and other unusual postures are often seen, especially in the face and shoulders.Weight loss and poor nutrition
Difficulty eating, swallowing, and controlling mouth movements can cause weight loss and malnutrition if not well managed.Autonomic and other systemic symptoms
Some patients may have low blood pressure, bowel or bladder changes, and other body-system problems, often in later disease stages, due to widespread nervous system involvement.Slow but progressive course
Symptoms usually get worse slowly over many years. Without a cure, people often become more disabled, needing help with walking, eating, and daily care.
Diagnostic Tests
Doctors diagnose Levine–Critchley syndrome / chorea-acanthocytosis by combining the story of symptoms, the physical examination, blood tests, electrical tests, imaging, and genetic tests. No single test alone is enough in every patient, but together they give a clear picture.
Physical Examination
Full neurological examination
The doctor carefully watches movements, checks muscle tone, looks for chorea, dystonia, tics, and trunk spasms, and tests walking and balance. The pattern of face-and-mouth movements plus limb chorea suggests a neuroacanthocytosis syndrome rather than some other movement disorder.Orofacial and oral cavity examination
The mouth is examined for tongue and cheek injuries, bite marks, and ulcers from repeated self-biting. These specific mouth signs, combined with abnormal orofacial movements, are very characteristic for this disease.Reflex testing
The doctor taps the knees and ankles to test tendon reflexes. Many patients show weak or absent reflexes because their peripheral nerves are damaged, helping to separate this disease from other purely brain-limited disorders.Mental status and cognitive examination
Simple bedside tests of memory, attention, language, and planning are used. Problems in these areas, together with movement signs, support the diagnosis of a neurodegenerative basal ganglia disease like chorea-acanthocytosis.
Manual / Bedside Tests
Speech and swallowing assessment
The doctor or speech therapist asks the person to speak, count, and swallow small sips of water or food. This shows how severe the dysarthria (speech problem) and dysphagia (swallowing problem) are, and helps guide nutrition and safety plans.Coordination and gait testing
Bedside tests such as finger-to-nose, heel-to-shin, turning in place, and walking in a straight line help measure balance and coordination. Abnormal results, combined with chorea, point to a basal ganglia and cerebellar involvement.Simple functional tests (activities of daily living)
Doctors may ask patients to button a shirt, write, or use utensils during an exam. Difficulty with these tasks shows how much the movement disorder has affected daily life and supports the diagnosis of a disabling hyperkinetic syndrome.
Laboratory and Pathological Tests
Peripheral blood smear for acanthocytes
A thin layer of blood is spread on a slide and viewed under a microscope. In this disease, a significant number of red blood cells have spiky edges (acanthocytes). While not always present, their detection is an important clue.Creatine kinase (CK) level
CK is a muscle enzyme measured in blood. Many patients have markedly raised CK because of ongoing muscle damage. This helps distinguish neuroacanthocytosis from some other movement disorders where CK is normal.Basic blood tests to rule out other causes
Doctors measure full blood count, liver function, thyroid function, glucose, and lipid profile to exclude other reasons for abnormal movements or acanthocytes, such as lipid disorders or thyroid disease. Normal lipoproteins with acanthocytes support neuroacanthocytosis.Serum and cerebrospinal fluid (CSF) studies in selected cases
Sometimes CSF is examined to exclude infections, autoimmune inflammation, or other neurological diseases. Normal CSF with typical clinical features directs doctors back toward a genetic neuroacanthocytosis diagnosis.Western blot for chorein protein
A special test on red blood cells can measure the chorein protein. In VPS13A disease, chorein is missing. This protein-based test is highly specific and helps confirm the diagnosis where available.Molecular genetic testing of VPS13A
The most important confirmatory test is DNA sequencing of the VPS13A gene. Finding harmful mutations in both copies of VPS13A gives a definite diagnosis, guides family counseling, and allows carrier testing.Expanded genetic panels or exome sequencing
When the diagnosis is unclear, larger gene panels for movement disorders or whole exome sequencing can identify VPS13A mutations or other related conditions, especially in families without clear history.
Electrodiagnostic Tests
Electroencephalogram (EEG)
EEG records brain electrical activity. In this disease, it may show epileptic discharges or generalized slowing. EEG helps confirm epilepsy and exclude some other seizure disorders.Electromyography (EMG)
EMG measures the electrical activity of muscles. It can show signs of myopathy (muscle disease) or neuropathy (nerve damage), which are both common in chorea-acanthocytosis and support the diagnosis of a neuroacanthocytosis syndrome.Nerve conduction studies (NCS)
This test checks how fast and how well electrical signals travel in peripheral nerves. Slowed or reduced signals in sensory and motor nerves confirm peripheral neuropathy, one of the characteristic features.
Imaging Tests
Brain MRI (magnetic resonance imaging)
MRI is the main imaging test. In many patients, it shows shrinkage (atrophy) of the caudate nucleus and putamen and widening of the front parts of the lateral ventricles. Sometimes there are signal changes in these regions. This pattern supports the diagnosis.Brain CT scan
CT is less detailed than MRI but can show brain atrophy, especially in the basal ganglia and cortical areas, in advanced disease. It may be used when MRI is not available or is contraindicated.Functional imaging (PET or SPECT) in special cases
Advanced imaging like PET or SPECT can show reduced metabolism or blood flow in basal ganglia and related regions, supporting the idea of a progressive neurodegenerative basal ganglia disorder when standard tests are unclear.
Non-Pharmacological Treatments
Regular care with a neurology team
A neurologist familiar with movement disorders and rare diseases should lead care. They monitor chorea, dystonia, seizures, mood, and swallowing over time, adjust treatments, and coordinate other specialists such as psychiatrists, physiotherapists, and dietitians. Close follow-up helps detect complications early, such as weight loss, aspiration pneumonia, or heart problems, and allows timely changes in the care plan.Physiotherapy for movement and balance
Physiotherapists design simple exercises to keep muscles strong, joints flexible, and balance as safe as possible. Training may include walking practice, posture correction, stretching, and task-specific training like getting in and out of a chair. This does not stop the disease, but it can delay loss of mobility, reduce falls, and help the person stay independent for longer.Occupational therapy for daily activities
Occupational therapists help the person adapt everyday tasks such as dressing, eating, washing, and writing. They may suggest special utensils, modified clothing, and ways to organize the home to reduce effort and risk. Their goal is to keep the person as independent as possible while reducing fatigue and caregiver strain.Speech and language therapy
Speech therapists work on slurred speech, vocalizations, and swallowing problems, which are very common in chorea-acanthocytosis. They teach safe swallowing strategies, recommend food textures, and sometimes suggest communication tools such as picture boards or apps. Early therapy can lower the risk of choking, improve nutrition, and help the person stay connected with family and friends.Swallowing and nutrition management
A swallowing (dysphagia) assessment by a speech therapist or specialist team checks how safely the person can eat and drink. Dietitians then adapt meals: softer textures, thickened fluids, high-calorie shakes, and frequent small meals. When swallowing becomes too risky, a feeding tube (PEG) may be recommended to prevent weight loss and aspiration pneumonia.Dental and oral care
Because tongue and lip biting are characteristic signs, regular dental care is essential. Dentists may adjust teeth surfaces, provide mouth guards, or repair damage caused by self-biting. Good oral hygiene reduces infections and pain, making eating and speaking more comfortable and lowering the risk of serious mouth injuries.Psychological counseling and psychotherapy
Anxiety, depression, personality changes, and even psychosis can appear early, sometimes before movement symptoms. Counseling, cognitive-behavioral therapy, and family therapy help patients and relatives cope with stress, grief, behavior changes, and social isolation. Emotional support can improve adherence to treatment and overall quality of life.Cognitive rehabilitation
Neuropsychologists or occupational therapists can provide simple memory aids, attention exercises, and problem-solving strategies. Tools like notebooks, phone reminders, and structured daily routines make it easier to manage appointments and tasks even when thinking and memory slowly worsen.Social work and disability support
Social workers help families access disability benefits, home help, mobility aids, respite services, and legal documents (such as power of attorney). They also help plan for future stages of the disease, including potential long-term care needs, which reduces uncertainty and stress.Assistive devices and home adaptations
Walkers, wheelchairs, grab bars, shower seats, and bed rails make movement safer as coordination worsens. Removing loose rugs, improving lighting, and installing ramps can strongly reduce fall risk. A safer environment prevents injuries and helps both the patient and caregivers feel more secure.Fall-prevention training
Physiotherapists can teach safe transfer techniques, use of supports, and ways to turn or stand without losing balance. Practicing “safe falling” and how to get up from the floor can reduce fear and serious injuries when slips do occur.Seizure safety education
For patients with seizures, families are taught what a seizure looks like, how to protect the person from injury, and when to call emergency services. Advice includes avoiding unsupervised swimming, taking showers instead of baths, and using helmets when needed. These simple steps lower the risk of serious accidents.Sleep hygiene and routine
Regular sleep–wake times, a quiet dark bedroom, limited late-evening screen use, and calming routines may improve sleep quality, which can be disturbed by involuntary movements and mood symptoms. Better sleep can also reduce daytime irritability and fatigue.Non-drug pain and stiffness management
Gentle stretching, warm baths, heat packs, massage, and relaxation techniques can ease muscle tension and discomfort from dystonia and contractures. These methods can be combined with medications but sometimes let doctors use lower drug doses, reducing side effects.Support groups and patient networks
Rare disease support groups (including neuroacanthocytosis foundations and EU/ERN-RND networks) connect families facing similar problems. Sharing experiences, practical tips, and research news helps people feel less alone and more empowered to take part in care decisions and clinical trials.Regular cardiac evaluation
Some neuroacanthocytosis syndromes, especially McLeod syndrome, can involve heart muscle disease and rhythm problems. Even in chorea-acanthocytosis, periodic heart checks (ECG, echocardiogram) are recommended to detect silent problems early and guide treatment if cardiomyopathy appears.Nutrition counseling for long-term energy needs
Because chorea and dystonia burn a lot of calories, weight loss is common. A dietitian can plan high-calorie, high-protein meals and snacks, including nutritional drinks, to maintain weight and muscle mass. Adjusting fiber and fluid intake also helps prevent constipation, which can worsen discomfort and mobility.Communication aids and technology
As speech becomes harder, the team may offer alphabet boards, text-to-speech apps, or simple symbol boards. These tools allow patients to express needs and feelings even when articulation is poor, preserving social relationships and dignity.Advance care planning and palliative care
Early discussions about patient wishes for future treatment, hospitalization, feeding tubes, and life-sustaining therapies are important. Palliative care teams focus on comfort, symptom relief, and family support at all stages, not only at the end of life. This planning respects the person’s values and reduces crisis decisions.Genetic counseling for family members
Because chorea-acanthocytosis is usually autosomal recessive due to VPS13A mutations, genetic counseling helps relatives understand inheritance, carrier testing, and prenatal or pre-implantation options. This does not change the patient’s disease but can guide family planning and reduce uncertainty for siblings and children.
Drug Treatments
Important: All medicines and doses must be chosen and adjusted by a specialist. Below are examples commonly discussed in literature for neuroacanthocytosis and similar movement disorders; many are off-label for Levine-Critchley syndrome itself.
Tetrabenazine (Xenazine®, VMAT2 inhibitor)
Tetrabenazine depletes dopamine in the brain to reduce chorea. It is FDA-approved for chorea in Huntington’s disease and is often used off-label for severe chorea in chorea-acanthocytosis. Typical dosing starts low (e.g., 12.5 mg/day) and is slowly increased while watching for depression, sleepiness, and parkinsonism, because the drug carries a boxed warning for depression and suicidality.Deutetrabenazine (Austedo®)
Deutetrabenazine is a newer VMAT2 inhibitor also approved for Huntington’s chorea. It has a longer half-life and may cause fewer fluctuations. Dosing usually starts at a low daily amount and is titrated up, with careful monitoring for mood changes and QT-interval effects. It is sometimes chosen when tetrabenazine is not tolerated, although use in Levine-Critchley is extrapolated, not specifically studied.Valbenazine (Ingrezza®)
Valbenazine is a VMAT2 inhibitor approved mainly for tardive dyskinesia, and more recently evaluated for Huntington’s chorea. By reducing abnormal dopamine signaling, it can lessen involuntary movements. A usual adult regimen begins at 40 mg once daily, increasing toward 80 mg daily if tolerated, but use in neuroacanthocytosis remains off-label and should be restricted to specialist care.Clozapine (Clozaril®, atypical antipsychotic)
Clozapine blocks dopamine and other receptors and may help both severe chorea and psychiatric symptoms such as psychosis or aggression. It carries serious risks including agranulocytosis and myocarditis, so frequent blood count monitoring is mandatory. Doses are started very low and slowly increased. Because of safety concerns, clozapine is reserved for severely affected patients under specialist supervision.Other atypical antipsychotics (e.g., risperidone, olanzapine, quetiapine)
These drugs are often used to control chorea, irritability, psychosis, and mood swings, based on experience in Huntington’s disease and neuroacanthocytosis reports. They block dopamine receptors, which can calm movements but may worsen parkinsonism or cause metabolic side effects. Doses are individualized, usually starting very low and slowly increasing while monitoring weight, glucose, and lipids.Botulinum toxin injections (type A)
Injection of botulinum toxin into overactive mouth, tongue, or neck muscles is a key treatment for orolingual dystonia and self-biting. The toxin temporarily blocks acetylcholine at the neuromuscular junction, weakening targeted muscles for about 3–4 months. This can reduce tongue injuries, jaw clenching, and feeding dystonia and is repeated as needed by experienced injectors.Trihexyphenidyl (anticholinergic for dystonia)
Trihexyphenidyl reduces acetylcholine activity and is often used for dystonia, including cases in neuroacanthocytosis. It is started at a small dose and slowly increased, balancing benefits against side effects like dry mouth, constipation, blurred vision, and confusion. The drug may be particularly helpful in younger patients who tolerate anticholinergic effects better.Baclofen (GABA-B agonist for spasticity/dystonia)
Baclofen enhances inhibitory GABA-B signaling in the spinal cord to relax muscles and reduce stiffness and dystonia. It can be given orally in several daily doses, starting low and titrating up, or as intrathecal baclofen via a pump in selected severe cases. Side effects include sleepiness, weakness, and low blood pressure, so careful adjustment is needed.Benzodiazepines (e.g., clonazepam, diazepam)
Benzodiazepines enhance GABA-A activity and can help with myoclonus, dystonia, anxiety, and sleep. Clonazepam is commonly used, starting at low doses at night and slowly increasing as needed. Long-term use risks tolerance, dependence, and falls, so doctors often combine small doses with other treatments rather than rely on high doses alone.Levetiracetam (Keppra® and related brands)
Levetiracetam is a widely used anti-seizure drug indicated for several seizure types. It has a relatively favorable interaction profile, so it is often chosen in rare diseases like neuroacanthocytosis with epilepsy. Dosing starts low and is gradually increased, with attention to mood changes or irritability, which can occasionally occur.Other antiepileptic drugs (e.g., valproate, lamotrigine)
Depending on seizure type, neurologists may use valproate, lamotrigine, carbamazepine, or other standard anti-seizure medicines. These drugs stabilize neuronal firing through effects on ion channels and neurotransmitters. Choice depends on seizure pattern, age, and comorbidities, and patients require regular monitoring for liver, blood, and skin side effects.Selective serotonin reuptake inhibitors (SSRIs, e.g., sertraline)
Depression and anxiety are frequent and can severely affect quality of life. SSRIs increase serotonin levels and are standard treatments for mood disorders. Doses are slowly increased while monitoring for interaction with other neuropsychiatric medicines and for side effects such as gastrointestinal upset, sleep changes, or, rarely, agitation.Mood stabilizers (e.g., valproate, carbamazepine, lithium)
When mood swings or bipolar-like patterns occur, mood stabilizers may be considered. They help steady highs and lows and can also assist with irritability or aggression. Each drug has important safety issues (for example, liver function and teratogenicity with valproate), so specialists carefully balance risks and benefits.Proton-pump inhibitors / reflux treatments
Severe dysphagia and abnormal movements may worsen reflux and risk of aspiration. Medications such as proton-pump inhibitors reduce stomach acid, improving heartburn and protecting the esophagus. They are part of a broader swallowing and nutrition plan, not a primary neurological therapy.Sialorrhea medicines (e.g., glycopyrrolate)
Drooling can be socially distressing and increase aspiration risk. Anticholinergic drugs like glycopyrrolate or low-dose atropine drops reduce saliva production. Because they can also cause dry mouth, constipation, and urinary retention, doses are kept as low as possible and adjusted frequently.Short-acting sedatives for procedures
Sometimes short-acting sedatives or anesthetic agents are needed to safely perform procedures like MRI, dental work, or PEG insertion in patients with severe movements. The anesthesiology team tailors dose and drug choice to minimize respiratory and cardiac risk, especially in those with possible cardiomyopathy.Analgesics for pain (paracetamol, NSAIDs, carefully selected)
Musculoskeletal pain from abnormal movements, falls, and contractures may respond to simple analgesics such as paracetamol, sometimes NSAIDs if kidney, stomach, and heart risks are low. These drugs do not treat the underlying disease but help maintain mobility and sleep when used cautiously under medical guidance.Antispasticity combinations (baclofen + benzodiazepine, under supervision)
In some cases, doctors combine low doses of baclofen and benzodiazepines to target both tonic and phasic components of abnormal movements. This strategy seeks better symptom control while keeping each individual drug dose lower, but it requires close monitoring to avoid excessive sedation, weakness, or breathing problems.Cardiac medications (beta-blockers, antiarrhythmics) when needed
If cardiomyopathy or arrhythmias develop, cardiologists may prescribe beta-blockers, ACE inhibitors, or other heart medicines. These drugs aim to preserve heart function, control rhythm, and reduce heart failure risk. They are tailored to standard cardiology guidelines rather than specific to Levine-Critchley syndrome.Clinical-trial or compassionate-use therapies
Some patients may be eligible for experimental medicines such as new VMAT2 inhibitors, neuroprotective agents, or gene-targeted therapies. These treatments are only available in clinical research settings with strict safety monitoring and should be discussed with experienced centers or rare-disease networks.
Dietary Molecular Supplements
Always discuss supplements with the care team to avoid interactions with prescribed drugs. Evidence is mainly general for brain and nerve health, not specific cures for Levine-Critchley syndrome.
Omega-3 fatty acids (fish oil, EPA/DHA) – May support brain cell membranes and reduce inflammation. Typical studied doses are around 1–3 g/day of combined EPA/DHA, taken with food to reduce stomach upset.
Vitamin D – Important for bone strength, muscle function, and immune regulation. Many people with chronic neurological illness are deficient. Doctors usually aim for replacement doses guided by blood levels to avoid toxicity.
B-complex vitamins (including B1, B6, B12, folate) – Support nerve function and energy metabolism. Supplementation is particularly important if diet is poor or malabsorption is present; doses vary from standard multivitamins to higher therapeutic doses under supervision.
Coenzyme Q10 – A mitochondrial cofactor studied in several neurodegenerative diseases. Typical supplemental doses range from 100–300 mg/day, but evidence for clear benefit is mixed, so it is usually considered optional and used only after discussing cost and possible benefits.
Vitamin E and other antioxidants – Act as free-radical scavengers and may support cell membrane stability. High-dose vitamin E can have bleeding risks, so clinicians usually recommend modest doses within safe daily limits.
Magnesium – Involved in nerve and muscle function. Some people use it for cramps, sleep, or constipation. Doses must be adjusted to avoid diarrhea or, in kidney disease, high blood magnesium.
N-acetylcysteine (NAC) – A precursor of glutathione, an important antioxidant. Research in various brain disorders suggests potential benefits on oxidative stress, but data in neuroacanthocytosis are lacking, so it is considered experimental supportive care only.
Alpha-lipoic acid – Another antioxidant sometimes used for neuropathy symptoms. It may help nerve pain in diabetic neuropathy and is occasionally tried for similar complaints here, with dosing around 300–600 mg/day under supervision.
Curcumin (turmeric extract) – Has anti-inflammatory and antioxidant properties. Absorption is higher in formulations combined with piperine or lipids. Because it can interact with blood thinners and affect gallbladder disease, medical advice is needed.
Probiotics and prebiotic fiber – Long-term medicines and immobility can disturb gut flora. Probiotic supplements and increased prebiotic fiber may improve bowel habits and overall gut health, which indirectly supports nutrition and comfort.
Immunity-Booster, Regenerative and Stem-Cell-Related Drugs (6 – Mostly Research Stage)
Intravenous immunoglobulin (IVIG)
IVIG is a pooled antibody product used for some autoimmune neurologic diseases. In Levine-Critchley syndrome, its role is not established, but it may be considered only if there is evidence of overlapping immune-mediated complications. Treatment is given in hospital, with careful monitoring for thrombosis, kidney problems, and headache.Erythropoietin derivatives (experimental neuroprotection)
Erythropoietin and related agents have shown neuroprotective effects in some animal models. For neuroacanthocytosis, this remains experimental, with any use restricted to clinical trials. Potential risks include high blood pressure and clotting, so self-medication is unsafe and not recommended.Mesenchymal stem-cell infusions
Various trials in neurodegenerative diseases are exploring mesenchymal stem-cell infusions as a way to deliver growth factors and modulate inflammation. There is no proven benefit for Levine-Critchley syndrome yet, and such therapies should only be accessed within regulated research programs, not commercial “stem-cell clinics.”Neural stem-cell transplantation
Transplanting neural stem cells to replace lost basal ganglia neurons is a theoretical approach similar to some Huntington’s disease research. At present, it is experimental, technically complex, and available only in specialized trials. It is not standard care and should not be offered outside strict ethical and regulatory frameworks.Gene-targeted therapies for VPS13A disease
Because chorea-acanthocytosis is caused by mutations in the VPS13A gene, scientists are exploring gene-replacement or gene-editing strategies in the laboratory. These approaches are still pre-clinical and not available as treatments, but they offer hope for future disease-modifying therapy once safety and effectiveness are proven.Growth-factor and neurotrophic-factor drugs
Experimental drugs that mimic or boost brain growth factors (such as BDNF or GDNF-like molecules) are under study in several movement disorders. In Levine-Critchley syndrome, there is no approved product yet, and use is limited to research. Families should discuss any trial opportunities with experienced centers or rare-disease networks.
Surgeries and Procedures
Deep brain stimulation (DBS) of the globus pallidus internus
DBS uses implanted electrodes to deliver electrical stimulation to deep brain structures. Case series in chorea-acanthocytosis show that DBS of the internal globus pallidus can reduce severe chorea, dystonia, self-injury, and feeding dystonia in some patients, though results vary. It is reserved for carefully selected individuals after medication options are optimized.Gastrostomy (PEG) tube insertion
When swallowing becomes unsafe and weight drops despite all strategies, a PEG feeding tube can be placed through the abdominal wall into the stomach. This procedure allows long-term nutritional support, reduces aspiration risk, and makes medication delivery easier, especially when mouth movements are severe.Dental and oral surgical procedures
Dental extractions, reshaping of teeth, or protective dental appliances may be needed to reduce tongue and lip biting. In extreme cases, surgery on jaw muscles may be considered. These procedures aim to prevent repeated bleeding, infections, and pain that can severely affect eating and quality of life.Orthopedic surgery for contractures or deformities
Long-standing abnormal postures and dystonia can cause fixed joint contractures and deformities. In selected patients, orthopedic surgery (such as tendon lengthening or joint release) may be considered to improve sitting, hygiene, or pain. It is usually combined with intensive physiotherapy after surgery.Cardiac device implantation (e.g., pacemaker)
If serious heart rhythm problems or conduction defects develop, especially in related neuroacanthocytosis syndromes, cardiologists may recommend a pacemaker or defibrillator. The goal is to prevent syncope and sudden cardiac death, following standard cardiology indications rather than disease-specific rules.
Prevention Strategies
Because Levine-Critchley syndrome is genetic, we cannot prevent the underlying mutation, but we can reduce complications:
Early diagnosis and referral to a specialist center to start symptom management and monitoring before severe weight loss or injuries occur.
Genetic counseling for relatives to inform carrier status, reproductive options, and early evaluation if symptoms appear.
Vaccination and infection prevention (e.g., influenza, pneumonia vaccines) to reduce pneumonia risk, especially with swallowing problems.
Regular dental and oral care to prevent mouth infections and damage from self-biting.
Aggressive fall-prevention measures (home safety, physiotherapy, assistive devices) to reduce fractures and head injuries.
Timely management of seizures to avoid status epilepticus and trauma.
Early swallowing assessment to prevent aspiration pneumonia and severe malnutrition.
Monitoring for mood changes and suicidality, especially when using VMAT2 inhibitors or antipsychotics, to prevent self-harm.
Regular cardiac evaluations to detect cardiomyopathy or arrhythmias before they cause sudden events.
Healthy lifestyle (nutrition, sleep, avoiding smoking and excess alcohol) to support general health and resilience against complications.
When to See Doctors
People with Levine-Critchley syndrome should have regular planned visits with their neurology team, usually every few months, and urgent review if new problems appear. Red-flag reasons to seek medical help include sudden worsening of swallowing or coughing during meals, rapid weight loss, new or more frequent seizures, chest pain, fainting, major behavior changes, suicidal thoughts, or new breathing difficulties. Caregivers should also contact doctors if movement becomes so severe that falls, injuries, or self-biting cannot be controlled at home, or if there are signs of infection such as fever, productive cough, or confusion.
Diet: What to Eat and What to Avoid
Focus on high-calorie, high-protein foods (eggs, fish, dairy, legumes, nut butters) to counteract energy loss from constant movements.
Use soft, moist textures (soups, stews, smoothies) if chewing and swallowing are difficult, based on the swallowing team’s advice.
Take frequent small meals and snacks to reduce fatigue and choking risk compared to large meals.
Ensure enough fluid intake with safe consistencies (sometimes thickened liquids) to prevent dehydration and constipation.
Include fiber from fruits, vegetables, and whole grains as tolerated, adjusting texture to avoid choking, to support bowel health.
Avoid very hard, dry, or crumbly foods (nuts, crackers, dry bread) that increase choking risk unless a therapist says they are safe.
Limit alcohol because it can worsen balance, mood, and interactions with medications.
Avoid crash diets or fasting, which can lead to rapid weight loss and weakness in a body already under stress.
Be cautious with herbal products that have unclear interactions with VMAT2 inhibitors, antipsychotics, or antiepileptics; always ask the doctor first.
Work closely with a dietitian who understands neurological disease and can adjust the plan as symptoms change over time.
Frequently Asked Questions
Is Levine-Critchley syndrome the same as chorea-acanthocytosis?
Today, most experts use the name chorea-acanthocytosis or VPS13A disease for the condition once called Levine-Critchley syndrome; it is part of the neuroacanthocytosis syndromes with similar features like chorea, acanthocytes in blood, and progressive neurological decline.What causes this disease?
The main cause is mutations in both copies of the VPS13A gene, inherited in an autosomal recessive pattern. The gene problem leads to lack of a protein called chorein, which is important for cell membrane and intracellular trafficking, especially in neurons and red blood cells.Is there a cure?
There is currently no cure or proven disease-modifying treatment. Management is supportive and focuses on reducing symptoms, preventing complications, and supporting the person and family. Research into gene-targeted and regenerative therapies is ongoing but still experimental.How is Levine-Critchley syndrome different from Huntington’s disease?
Both can cause chorea and behavior changes, but the genetics, blood findings, and detailed brain changes differ. In neuroacanthocytosis, acanthocytes appear in blood, and the responsible gene is usually VPS13A, while Huntington’s disease is caused by a CAG repeat expansion in the HTT gene.What ages are affected?
Symptoms often start in early or middle adulthood, but can appear earlier or later. There is usually slow progression over years or decades, so early recognition and long-term planning are important for families.Can my children get the disease?
If you have chorea-acanthocytosis due to recessive VPS13A mutations, each child will inherit at least one mutated gene. The exact risk that a child will be affected depends on your partner’s carrier status; genetic counseling and testing are needed to calculate the risk and discuss options.What tests are used to diagnose it?
Doctors use clinical examination, blood smear for acanthocytes, blood tests such as CK, brain MRI, and sometimes Western blot showing lack of chorein. Definitive diagnosis usually requires genetic testing for VPS13A mutations. Other neuroacanthocytosis syndromes and Huntington’s disease are also checked in the differential diagnosis.Can people with this condition work or study?
Many people can continue work or study in early stages with accommodations such as flexible schedules, adapted computers, and support with communication. As the disease progresses, jobs may need to change or stop, but rehabilitation teams can help plan realistic goals and training.Is exercise safe?
Gentle, supervised exercise is usually encouraged to maintain strength, flexibility, and mood, provided safety measures are in place to prevent falls. Sudden intense exertion or unsupervised risky activities should be avoided, especially if balance, seizures, or heart problems are present.Do all patients get seizures?
No. Some patients develop seizures, while others never do. If seizures occur, they are treated with standard anti-seizure medicines and safety advice, and often respond reasonably well to therapy.How long do people live with Levine-Critchley syndrome?
Life expectancy varies and depends greatly on complications such as aspiration pneumonia, severe weight loss, infections, and cardiac issues. With careful multidisciplinary care, some people live for decades after symptom onset, but the disease remains serious and ultimately progressive.Can pregnancy be safe?
Pregnancy in someone with neuroacanthocytosis needs close management by neurology and high-risk obstetrics teams. Medicines may need adjustment for safety, and physical limitations can complicate care. Pre-pregnancy counseling is very important to discuss genetic risks, maternal health, and realistic plans.Are there international expert centers or networks?
Yes. European Reference Networks (ERN-RND), specialized movement-disorder clinics, and neuroacanthocytosis foundations provide expertise, clinical-trial information, and support resources, often linking patients across countries. Asking a local neurologist for referral to such centers can be helpful.What should caregivers know most of all?
Caregivers should learn about symptom patterns, medication side effects, safe feeding and transfer techniques, and signs that need urgent medical review. They should also seek support for themselves, because long-term caring is physically and emotionally demanding and they deserve structured help and respite.Where can we find trustworthy information?
Reliable sources include GeneReviews, national neurology organizations, rare-disease registries, and peer-reviewed articles rather than random web pages or commercial “cure” offers. Your neurology team can recommend specific websites and patient organizations recognized by experts.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 14, 2026.
