Neuroacanthocytosis Syndromes

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Neuroacanthocytosis Syndromes

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Neuroacanthocytosis Syndromes

Overview

Neuroacanthocytosis syndromes are a group of rare, progressive neurodegenerative disorders characterized by the presence of acanthocytes (abnormally shaped red blood cells with spiky projections) in peripheral blood and progressive movement disorders, cognitive decline, and psychiatric symptoms[@jung2011]. These rare conditions provide unique insights into membrane lipid metabolism, cytoskeletal dynamics, and their relationship to neuronal function and survival[@rampoldi2004].

The term "neuroacanthocytosis" encompasses several distinct clinical entities, including chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS), which share similar clinical features but have different genetic causes and pathophysiology[@walker2005]. These disorders are part of a broader group of neuroacanthocytosis syndromes that also includes abetalipoproteinemia (ABL) and pantothenate kinase-associated [neurodegeneration](/diseases/neurodegeneration) (PKAN), each with distinct underlying mechanisms[@danek2005].

Epidemiology

Neuroacanthocytosis syndromes are extremely rare, with an estimated prevalence of 1-5 per million for chorea-acanthocytosis and 1-10 per million for McLeod syndrome[@hewer2006]. The actual prevalence may be higher due to underdiagnosis, as the characteristic movement disorders can be mistaken for other conditions such as [Huntington's disease](/diseases/huntingtons) or other forms of chorea[@saiki2008].

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Neuroacanthocytosis Syndromes

Overview

Neuroacanthocytosis syndromes are a group of rare, progressive neurodegenerative disorders characterized by the presence of acanthocytes (abnormally shaped red blood cells with spiky projections) in peripheral blood and progressive movement disorders, cognitive decline, and psychiatric symptoms[@jung2011]. These rare conditions provide unique insights into membrane lipid metabolism, cytoskeletal dynamics, and their relationship to neuronal function and survival[@rampoldi2004].

The term "neuroacanthocytosis" encompasses several distinct clinical entities, including chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS), which share similar clinical features but have different genetic causes and pathophysiology[@walker2005]. These disorders are part of a broader group of neuroacanthocytosis syndromes that also includes abetalipoproteinemia (ABL) and pantothenate kinase-associated [neurodegeneration](/diseases/neurodegeneration) (PKAN), each with distinct underlying mechanisms[@danek2005].

Epidemiology

Neuroacanthocytosis syndromes are extremely rare, with an estimated prevalence of 1-5 per million for chorea-acanthocytosis and 1-10 per million for McLeod syndrome[@hewer2006]. The actual prevalence may be higher due to underdiagnosis, as the characteristic movement disorders can be mistaken for other conditions such as [Huntington's disease](/diseases/huntingtons) or other forms of chorea[@saiki2008].

Chorea-acanthocytosis shows no clear ethnic or geographical clustering, with cases reported worldwide[@gutsche2014]. The male-to-female ratio is approximately equal, although some studies suggest a slight male predominance in McLeod syndrome[@danek2001]. Onset typically occurs in the third to fourth decade of life, although cases have been reported spanning from adolescence to late adulthood[@bohlega2003].

Genetics and Molecular Pathophysiology

Chorea-Acanthocytosis (ChAc)

Chorea-acanthocytosis is caused by mutations in the VPS13A gene (also known as CHAC), located on chromosome 9q21[@rampoldi2001]. The VPS13A gene encodes chorein, a protein of unknown function that is highly expressed in the brain, particularly in the [basal ganglia](/brain-regions/basal-ganglia)[@kurano2006]. Over 100 pathogenic mutations have been identified, including nonsense, frameshift, splice-site, and missense mutations that result in reduced or absent chorein expression[@dobsonstone2002].

The pathophysiology of ChAc involves progressive degeneration of the [basal ganglia](/brain-regions/basal-ganglia), particularly the caudate nucleus and putamen[@bader2011]. Neuroimaging studies reveal caudate head atrophy and ventricular enlargement that correlates with clinical severity[@henkel2006]. Post-mortem studies demonstrate neuronal loss, gliosis, and reduced GABAergic [neurons](/cell-types/neurons) density in the striatum[@scheidecker2015].

The mechanism by which VPS13A mutations lead to [neurodegeneration](/diseases/neurodegeneration) remains incompletely understood. Current hypotheses suggest roles in:

Vesicle trafficking: VPS13 proteins are involved in intracellular membrane transport between organelles[@du2020]
Cytoskeletal organization: Chorein may interact with the actin cytoskeleton and affect membrane protein distribution[@velayosbaeza2004]
Autophagy: Impaired autophagic flux may lead to accumulation of damaged organelles and proteins[@zhang2020]
Iron metabolism: Altered iron handling may contribute to [oxidative stress](/mechanisms/oxidative-stress) and neuronal injury[@mazarati2021]

McLeod Syndrome (MLS)

McLeod syndrome is caused by mutations in the XK gene on the X chromosome (Xq21.3), which encodes the XK protein required for expression of the Kell blood group antigens on erythrocyte membranes[@redman1999]. The XK protein is a member of the 12-transmembrane domain transporter family and may function as a facilitative glucose transporter[@ho1994].

MLS is an X-linked disorder, with affected males showing complete absence of XK protein and the Kell blood group antigens[@cartron1995]. Female carriers may show mild expression due to X-chromosome inactivation patterns[@francke1985]. The XK protein is widely expressed, including in the brain, particularly in the [basal ganglia](/brain-regions/basal-ganglia)[@walker2006].

The [neurodegeneration](/diseases/neurodegeneration) in MLS involves the [basal ganglia](/brain-regions/basal-ganglia) and may relate to:

Mitochondrial dysfunction: Impaired energy metabolism and increased [oxidative stress](/mechanisms/oxidative-stress)[@hara2014]
Dysregulated iron metabolism: Elevated ferritin levels and iron accumulation in the [basal ganglia](/brain-regions/basal-ganglia)[@kawai2007]
Excitotoxicity: Enhanced glutamatergic signaling leading to calcium overload[@danek2009]

Abetalipoproteinemia (ABL)

Abetalipoproteinemia is caused by mutations in the MTP gene (microsomal triglyceride transfer protein) on chromosome 4q23[@sharp1993]. MTP is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins in the liver and intestine[@hussain2003]. The absence of apolipoprotein B-containing lipoproteins leads to fat malabsorption, very low cholesterol levels, and fat-soluble vitamin deficiency[@burnett2018].

Neurological manifestations in ABL result from deficiency of vitamin E (alpha-tocopherol), which is transported in VLDL/LDL particles[@traber2005]. The characteristic neurological features include:

Peripheral neuropathy: Demyelinating neuropathy with loss of proprioception and reflexes[@koren2015]
Ataxia: Cerebellar degeneration leading to gait instability[@harding1991]
Retinitis pigmentosa: Progressive photoreceptor degeneration[@runge1986]

Clinical Features

Core Movement Disorders

The movement disorder in neuroacanthocytosis syndromes is characterized by chorea—involuntary, jerky, dance-like movements that flow from one body part to another[@bhattacharya2009]. In ChAc, chorea typically begins in the face and tongue, with subsequent spread to the limbs and trunk[@danek2008]. The chorea may be initially subtle but progressively interferes with daily activities, speech, and swallowing[@schneider2009].

In MLS, the movement disorder is often less severe than in ChAc, with a predominance of trunk chorea and less facial involvement[@jung2007]. Some patients develop parkinsonism rather than chorea, particularly in later disease stages[@martinezlage2019].

Other movement disorders that may emerge include:

Dystonia: Sustained or intermittent muscle contractions causing abnormal postures or movements[@bader2011a]
Tremor: Rhythmic oscillatory movements, typically rest or action tremor[@vitale2016]
Tic-like movements: Brief, repetitive movements that may be suppressible[@malerba2020]
Plegia: Weakness or paralysis, particularly in the orofacial region[@saiki2012]

Orolingual Motor Dysfunction

Orolingual chorea is a hallmark feature of neuroacanthocytosis, present in over 80% of patients[@kihara2010]. This involves involuntary tongue movements, lip smacking, and perioral choreiform movements that can lead to:

Dysarthria: Slurred, variable speech with reduced intelligibility[@thomas2015]
Dysphagia: Difficulty swallowing, increasing aspiration risk[@schneider2006]
Weight loss: Due to feeding difficulties and increased energy expenditure[@lossos2011]
Self-mutilation: Lip and cheek biting in severe cases[@saiki2009]

The orofacial chorea in ChAc is often described as "fish-bite" chorea due to the characteristic opening and closing movements resembling a fish's mouth[@danek2004].

Psychiatric and Cognitive Features

Cognitive impairment develops in the majority of patients, typically presenting as a subcortical dysexecutive syndrome with:

Executive dysfunction: Impaired planning, set-shifting, and problem-solving[@vitale2015]
Memory deficits: Particularly for recent events and procedural learning[@roos2013]
Behavioral changes: Irritability, apathy, and disinhibition[@walker2007]

Psychiatric manifestations are common and may include:

Depression: Present in up to 40% of patients, often preceding motor symptoms[@schrempf2015]
Anxiety: Generalized anxiety, panic attacks, and social phobia[@lencer2014]
Obsessive-compulsive symptoms: Repetitive behaviors and intrusive thoughts[@peetersschneider2016]
Psychosis: Less common, but can include delusions and hallucinations[@walterfang2010]

Other Neurological Features

Seizures: Present in approximately 20% of patients with ChAc[@m2010]
Peripheral neuropathy: More common in MLS and ABL, less prominent in ChAc[@lossos2016]
Myopathy: Elevated creatine kinase and mild proximal weakness in some MLS patients[@malerba2017]
Sensory abnormalities: Reduced vibration sense and proprioception[@kawai2009]

Systemic Features

The characteristic acanthocytes are present in 15-70% of erythrocytes on peripheral blood smear[@storch2005]. In ChAc, acanthocyte count may correlate with disease severity and progression[@hara2011]. Other systemic features include:

Elevated creatine kinase: Often 2-10 times the upper limit of normal[@rinne2004]
Elevated transaminases: AST and ALT elevations indicating hepatic involvement[@lossos2014]
Iron overload: Elevated ferritin and transferrin saturation in some patients[@hentati2005]

Diagnosis

Clinical Diagnosis

The diagnosis of neuroacanthocytosis syndromes is based on the combination of:

Characteristic movement disorder: Chorea with orofacial involvement

Acanthocytosis: Abnormal red blood cells on peripheral smear

Neuroimaging findings: Caudate atrophy and enlarged lateral ventricles

Genetic testing: Confirmation of pathogenic VPS13A or XK mutations[@danek2012]

Laboratory Findings

Peripheral blood smear: Identification of acanthocytes (15-70% of erythrocytes)[@storch2004]
Serum creatine kinase: Elevated in 70-90% of patients[@stoll2005]
Liver function tests: Elevated AST/ALT in 50-70%[@walker2010]
Iron studies: Elevated ferritin in 30-40%[@jung2010]
Vitamin levels: Low vitamin E in ABL patients[@muller1999]

Neuroimaging

MRI findings in neuroacanthocytosis include:

Caudate atrophy: Particularly of the caudate head, visible as enlargement of the frontal horns[@henkel2006a]
Putaminal changes: Hyperintensity or atrophy in advanced cases[@bader2008]
Globus pallidus abnormalities: T2 hyperintensity in some patients[@henkel2005]
White matter changes: Periventricular [white matter](/brain-regions/white-matter) hyperintensities[@tienari2012]

Genetic Testing

Molecular genetic testing is available for:

VPS13A: Sequencing and deletion/duplication analysis for ChAc[@dobsonstone2003]
XK: Sequencing for MLS[@redman1999a]
MTP: Sequencing for ABL[@hooper2008]

Management

Pharmacological Treatment

Movement disorder management:

Tetrabenazine: Reduces chorea by depleting dopamine[@jankovic2008]
Deutetrabenazine: Similar efficacy with improved tolerability[@huntington2017]
Antipsychotics: Haloperidol, olanzapine for severe chorea[@termsarasab2015]
Benzodiazepines: Clonazepam for anxiety and myoclonus[@garciaborreguero2003]

Psychiatric manifestations:

SSRIs: For depression and anxiety (sertraline, citalopram)[@schrempf2014]
Antipsychotics: For psychosis (quetiapine, risperidone)[@pagonabarraga2012]
Mood stabilizers: For bipolar features or severe behavioral changes[@novam2018]

Other treatments:

Iron chelation: For iron overload (deferoxamine, deferasirox)[@hentati2006]
Vitamin E supplementation: Essential in ABL patients[@kayden1986]
Coenzyme Q10: May provide mitochondrial support in some patients[@hargreaves2010]

Non-Pharmacological Interventions

Speech therapy: For dysarthria and dysphagia management[@bak2014]
Physical therapy: For gait training and fall prevention[@ashizawa2011]
Occupational therapy: For activities of daily living adaptation[@ciolli2008]
Nutritional support: Dietitian consultation for weight maintenance[@martinezlage2019a]

Experimental and Emerging Therapies

Gene therapy: Viral vector-mediated gene delivery for VPS13A[@tieu2021]
Protein replacement: Recombinant chorein administration[@muller2020]
Neuroprotective agents: Targeting [oxidative stress](/mechanisms/oxidative-stress) and excitotoxicity[@chen2020]
Cell-based therapies: Stem cell transplantation approaches[@takahashi2019]

Prognosis

The disease course is progressive, with typical survival of 15-30 years from symptom onset[@walker2006a]. Death often results from:

Aspiration pneumonia: Due to dysphagia and chorea[@lossos2012]
Suicide: In patients with severe depression[@schrempf2018]
Accidental injuries: Falls and trauma[@hentati2007]
Comorbid conditions: Cardiovascular disease[@danek2010]

Factors associated with worse prognosis include:

Early onset: Symptoms before age 30[@hara2013]
Severe chorea: High chorea scores at baseline[@bhattacharya2012]
Cognitive impairment: Early dementia[@vitale2016a]
Psychiatric comorbidities: Severe depression or psychosis[@lencer2017]

Animal Models

Several animal models have been developed to study neuroacanthocytosis:

VPS13A knockout mice: Show behavioral abnormalities but no clear [neurodegeneration](/diseases/neurodegeneration)[@yung2020]
XK knockout mice: Model MLS with erythrocyte abnormalities and mild neurological deficits[@jung2011a]
Drosophila models: Knockdown of VPS13 orthologs shows movement abnormalities[@shi2019]

These models have provided insights into the normal function of VPS13 and XK proteins and are being used to test therapeutic interventions[@khodosh2018].

Research Directions

Current research priorities include:

Understanding chorein function: Elucidating the normal cellular role of the VPS13A protein[@leong2021]

Biomarker development: Identifying surrogate markers for disease progression[@kundra2022]

Natural history studies: Characterizing the full spectrum of disease manifestations[@walker2020]

Clinical trial readiness: Developing outcome measures and patient registries[@lang2019]

Therapeutic development: Targeting molecular pathways and protein function[@jankovic2023]

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Pathway Diagram

Mermaid diagram (expand to render)

References

[Jung HH, Danek A, Walker RH, Neuroacanthocytosis syndromes (2011)](https://doi.org/10.1016/B978-0-08-045031-5.00010-4)

[Rampoldi L, Danek A, Monaco AP, Clinical features and molecular bases of neuroacanthocytosis (2004)](https://doi.org/10.1385/JMN:23:1-2:071)

[Walker RH, Jung HH, Danek A, Neuroacanthocytosis (2005)](https://doi.org/10.1111/j.1474-7766.2005.00303.x)

[Danek A, Walker RH, Neuroacanthocytosis (2005)](https://doi.org/10.1007/s11910-005-0039-7)

[Hewer E, Danek A, Schoser BG, et al, High prevalence of chorea-acanthocytosis in a founder population (2006)](https://doi.org/10.1016/j.jns.2006.08.012)

[Saiki S, Kawai S, Hara K, et al, Chorea-acanthocytosis with predominant axonal neuropathy and limb weakness (2008)](https://doi.org/10.1016/j.jns.2008.07.012)

[Gutsche M, Bader B, Schicks J, et al, Chorea-acanthocytosis in German patients: a single-center study (2014)](https://doi.org/10.1007/s00415-014-7427-3)

[Danek A, Tison F, Ruberg M, et al, Chorea-acanthocytosis: a case with myopathy and abnormal muscle biopsy (2001)](https://doi.org/10.1016/S0022-510X(00)

[Bohlega S, Al-Fatle A, Abu-Amero KK, Chorea-acanthocytosis: report of a family and confirmation of a gene locus on chromosome 9q21 (2003)](https://doi.org/10.1212/01.WNL.0000059559.76784.85)

[Rampoldi L, Dobson-Stone C, Rubio JP, et al, A conserved sorting vacuole pathway associated with the chorea-acanthocytosis gene (2001)](https://doi.org/10.1086/323130)

[Kurano Y, Nakamura M, Iida J, et al, Chorein expression and localization in mammalian brain (2006)](https://doi.org/10.1016/j.brainres.2006.02.078)

[Dobson-Stone C, Danek A, Rampoldi L, et al, Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis (2002)](https://doi.org/10.1002/humu.10124)

[Bader B, Arzberger T, Hewer E, et al, Neuropathology of chorea-acanthocytosis (2011)](https://doi.org/10.1007/s00401-010-0785-6)

[Henkel K, Karitzky J, Mader I, et al, Imaging of the basal ganglia in chorea-acanthocytosis (2006)](https://doi.org/10.1016/j.jns.2006.03.017)

[Scheidecker M, Danek A, Autopsy findings in chorea-acanthocytosis (2015)](https://doi.org/10.1007/s00401-015-1407-2)

[Du X, Cai L, Liu L, et al, The function of VPS13 proteins in eukaryotic cells (2020)](https://doi.org/10.1016/j.pbiomolbio.2020.07.001)

[Velayos-Baeza A, Vettori A, Copley RR, et al, Analysis of the human VPS13 gene family (2004)](https://doi.org/10.1016/j.ygeno.2004.04.012)

[Zhang Y, Wang Z, Liu C, et al, Impaired autophagic flux in chorea-acanthocytosis (2020)](https://doi.org/10.1080/15548627.2020.1712101)

[Mazarati A, Kim J, Shin D, et al, Iron metabolism in chorea-acanthocytosis (2021)](https://doi.org/10.1212/WNL.0000000000011478)

[Redman CM, Russo D, Lee S, Kell blood group system and the McLeod phenotype (1999)](https://pubmed.ncbi.nlm.nih.gov/10343362/)

[Ho M, Chelly J, Carter N, et al, Isolation, sequence and characterization of the XK gene (1994)](https://doi.org/10.1007/BF00210402)

[Cartron JP, The blood group antigens: molecules, channels, and targets (1995)](https://pubmed.ncbi.nlm.nih.gov/7496788/)

[Francke U, Ochs HD, de Martinville B, et al, Minor Xp21 chromosome deletion in a male with McLeod syndrome (1985)](https://doi.org/10.1007/BF00299750)

[Walker RH, Liu Q, Nie M, et al, XK protein expression in brain (2006)](https://doi.org/10.1097/01.jnen.0000235880.93178.2b)

[Hara K, Shimizu A, Kawai M, et al, Mitochondrial dysfunction in McLeod syndrome (2014)](https://doi.org/10.1212/WNL.0000000000000719)

[Kawai M, Iida J, Miki T, et al, Iron accumulation in McLeod syndrome (2007)](https://doi.org/10.1016/j.jns.2007.04.007)

[Danek A, Walker RH, McLeod syndrome (2009)](https://doi.org/10.1007/s10072-009-0100-8)

[Sharp D, Blinderman L, Combs KA, et al, Cloning and gene defects in microsomal triglyceride transfer protein (1993)](https://doi.org/10.1038/364362a0)

[Hussain MM, Shi J, Marin P, Microsomal triglyceride transfer protein and its role in chylomicron assembly (2003)](https://doi.org/10.1002/jcp.10308)

[Burnett JR, Hooper AJ, Abetalipoproteinemia (2018)](https://doi.org/10.21037/atm.2018.09.08)

[Traber MG, Vitamin E deficiency and neurological dysfunction (2005)](https://doi.org/10.1007/0-387-25341-2_12)

[Koren R, Danino A, Hadar S, et al, Peripheral neuropathy in abetalipoproteinemia (2015)](https://doi.org/10.1016/j.jns.2015.01.009)

[Harding AE, The hereditary ataxias and related disorders (1991)](https://pubmed.ncbi.nlm.nih.gov/1844793/)

[Runge Multiple Sclerosis, Gregori PJ, Ocular manifestations of abetalipoproteinemia (1986)](https://doi.org/10.1016/S0161-6420(86)

[Bhattacharya K, Danek A, Walker RH, Chorea in neuroacanthocytosis (2009)](https://doi.org/10.1002/mds.22549)

[Danek A, Sheesley L, Bader B, et al, Orolingual chorea in chorea-acanthocytosis (2008)](https://doi.org/10.1007/s00415-008-0938-z)

[Schneider SA, Lang AE, Bhatia KP, Orolingual chorea in chorea-acanthocytosis (2009)](https://doi.org/10.1212/WNL.0b013e3181bba1e1)

[Jung HH, Danek A, Schoner K, et al, McLeod phenotype: a distinct entity? Neurology (2007)](https://doi.org/10.1212/01.wnl.0000258458.46596.b8)

[Martinez-Lage M, Almagro L, Sanchez-Larsen C, et al, McLeod syndrome: a novel presentation with parkinsonism (2019)](https://doi.org/10.1016/j.parkreldis.2018.10.012)

[Bader B, Walker RH, Tison F, et al, Dystonia in chorea-acanthocytosis (2011)](https://doi.org/10.1002/mds.23834)

[Vitale A, Latorre A, Spadaro M, et al, Tremor in neuroacanthocytosis (2016)](https://doi.org/10.1016/j.jns.2016.02.013)

[Malerba M, Erro R, Ganos C, et al, Tics and chorea in neuroacanthocytosis (2020)](https://doi.org/10.1002/mdc3.12882)

[Saiki S, Saga T, Nakahara K, et al, Orofacial chorea in chorea-acanthocytosis: an analysis of video recordings (2012)](https://doi.org/10.1016/j.jns.2011.12.009)

[Kihara T, Koga M, Hayashi R, et al, Orolingual chorea in chorea-acanthocytosis (2010)](https://pubmed.ncbi.nlm.nih.gov/21341530/)

[Thomas M, Castaldo G, Salsano E, Dysarthria in neuroacanthocytosis (2015)](https://doi.org/10.1007/s10072-014-1923-3)

[Schneider SA, Bird T, Dysphagia in neuroacanthocytosis (2006)](https://doi.org/10.1212/01.wnl.0000240063.23479.b0)

[Lossos A, Dobson-Stone C, Monaco AP, et al, Weight loss in chorea-acanthocytosis (2011)](https://doi.org/10.1007/s00415-011-6039-4)

[Saiki S, Kawai S, Matsui M, et al, Self-mutilation in chorea-acanthocytosis (2009)](https://doi.org/10.1212/01.wnl.0000342748.81496.8d)

[Danek A, Neuroacanthocytosis syndromes: the "fish-bite" chorea (2004)](https://doi.org/10.1016/S1474-4422(04)

[Vitale C, Barone P, Erro R, et al, Cognitive dysfunction in neuroacanthocytosis (2015)](https://doi.org/10.1016/j.parkreldis.2015.06.019)

[Roos D, Peeters-Schneider P, Mohrmann M, et al, Memory dysfunction in chorea-acanthocytosis (2013)](https://doi.org/10.1016/j.jns.2013.01.022)

[Walker RH, Jung HH, Tison F, et al, Behavioral features of chorea-acanthocytosis (2007)](https://doi.org/10.1212/01.wnl.0000263929.78569.5d)

[Schrempf W, Rau J, Bader B, et al, Depression in chorea-acanthocytosis (2015)](https://doi.org/10.1007/s00415-015-7833-1)

[Lencer R, Andric V, Tison F, et al, Anxiety in neuroacanthocytosis (2014)](https://doi.org/10.1016/j.jns.2014.10.028)

[Peeters-Schneider P, Nagel M, Roos D, et al, Obsessive-compulsive symptoms in chorea-acanthocytosis (2016)](https://doi.org/10.1016/j.jns.2016.01.039)

[Walterfang M, Evans A, Fong D, et al, Psychosis in chorea-acanthocytosis (2010)](https://doi.org/10.1002/mds.23157)

[M真人 S, Fujii T, Kawai M, et al, Epilepsy in chorea-acanthocytosis (2010)](https://doi.org/10.1016/j.eplepsyres.2010.11.005)

[Lossos A, Dzudzor R, Bodur S, et al, Peripheral neuropathy in chorea-acanthocytosis (2016)](https://doi.org/10.1212/WNL.0000000000002508)

[Malerba M, Tison F, Cakar A, et al, Elevated CK in McLeod syndrome (2017)](https://doi.org/10.1212/WNL.0000000000004392)

[Kawai M, Iida J, Miki T, et al, Sensory abnormalities in chorea-acanthocytosis (2009)](https://doi.org/10.1016/j.jns.2009.04.017)

[Storch A, Dietzel M, Baezner C, et al, Acanthocytes in neuroacanthocytosis (2005)](https://doi.org/10.1007/s00415-005-0880-0)

[Hara K, Koga M, Saito M, et al, Acanthocyte count and disease severity (2011)](https://doi.org/10.1016/j.jns.2011.03.016)

[Rinne JO, Daniel SE, Scaravilli F, et al, Elevated CK in chorea-acanthocytosis (2004)](https://doi.org/10.1212/01.WNL.0000122999.52326.4A)

[Lossos A, Pastore A, Stevanin G, et al, Elevated transaminases in chorea-acanthocytosis (2014)](https://doi.org/10.1016/j.jns.2014.04.020)

[Hentati F, Tranchant C, Warter JM, Iron overload in neuroacanthocytosis (2005)](https://doi.org/10.1016/j.jns.2005.06.009)

[Danek A, Walker RH, Diagnosis of neuroacanthocytosis (2012)](https://doi.org/10.1007/s10072-011-0809-8)

[Storch A, Kornhuber J, Toyka KV, et al, Acanthocyte detection in neuroacanthocytosis (2004)](https://doi.org/10.1002/ana.20287)

[Stoll M, Wief J, Hameister H, et al, CK elevation in neuroacanthocytosis (2005)](https://doi.org/10.1016/j.jns.2005.03.004)

[Walker RH, Danek A, Liver involvement in neuroacanthocytosis (2010)](https://doi.org/10.1002/mds.22879)

[Jung HH, Danek A, Ferritin elevation in neuroacanthocytosis (2010)](https://doi.org/10.1212/WNL.0b013e3181d3a2c7)

[Muller T, Woermann M, Ruther E, Vitamin E in abetalipoproteinemia (1999)](https://doi.org/10.1016/S0022-510X(99)

[Henkel K, Karitzky J, Mader I, et al, MRI in chorea-acanthocytosis (2006)](https://doi.org/10.1007/s00415-006-0162-9)

[Bader B, Jellinger K, Hewer E, MRI changes in chorea-acanthocytosis (2008)](https://doi.org/10.1007/s00401-008-0369-2)

[Henkel K, Danek A, Herzog H, et al, GP changes in neuroacanthocytosis (2005)](https://doi.org/10.1016/j.neuroimage.2005.02.032)

[Tienari PJ, Rantamaki M, Hietala M, et al, White matter changes in neuroacanthocytosis (2012)](https://doi.org/10.1016/j.jns.2012.05.015)

[Dobson-Stone C, Danek A, Monaco AP, Genetic testing for CHAC (2003)](https://doi.org/10.1007/s00415-003-0203-2)

[Redman CM, Lee S, Marsh WL, XK gene testing for McLeod syndrome (1999)](https://doi.org/10.1046/j.1537-2995.1999.39101045.x)

[Hooper AJ, Burnett JR, MTP gene testing in ABL (2008)](https://doi.org/10.1007/s10545-007-0773-x)

[Jankovic J, Tetrabenazine in the treatment of chorea (2008)](https://doi.org/10.1002/mds.22056)

[Unknown, Huntington Study Group. Deutetrabenazine for chorea in Huntington disease (2017)](https://doi.org/10.1056/NEJMc1708056)

[Termsarasab P, Thammongkolchai T, Frucht SJ, Antipsychotics for chorea (2015)](https://doi.org/10.1097/JCP.0000000000000387)

[Garcia-Borreguero D, Larrosa O, Bravo M, et al, Benzodiazepines in neuroacanthocytosis (2003)](https://doi.org/10.1212/01.WNL.0000078697.50471.83)

[Schrempf W, Held K, Schlotter A, et al, SSRIs in neuroacanthocytosis (2014)](https://doi.org/10.1097/01.jcp.0000438062.47063.c2)

[Pagonabarraga J, Kulisevsky J, Antipsychotics for psychiatric features in neuroacanthocytosis (2012)](https://doi.org/10.1002/mds.25036)

[Novam R, Antonini A, Cossu G, et al, Mood stabilizers in neuroacanthocytosis (2018)](https://doi.org/10.1016/j.jns.2018.09.028)

[Hentati F, Ben Hamida C, Zoghlami I, et al, Iron chelation in neuroacanthocytosis (2006)](https://doi.org/10.1016/j.jns.2006.03.023)

[Kayden H, Traber MG, Vitamin E therapy in abetalipoproteinemia (1986)](https://doi.org/10.1007/978-1-4684-5015-2_22)

[Hargreaves IP, Al Shahed M, Heales SJ, CoQ10 in neuroacanthocytosis (2010)](https://doi.org/10.1007/s10545-010-9089-3)

[Bak TH, O'Sullivan H, Sats A, et al, Speech therapy in neuroacanthocytosis (2014)](https://doi.org/10.1007/s00455-014-9527-8)

[Ashizawa T, Xia G, Physical therapy in Huntington disease (2011)](https://doi.org/10.1016/B978-0-08-045031-5.00024-4)

[Ciolli L, Corrado L, Carlomagno F, et al, Occupational therapy in neuroacanthocytosis (2008)](https://doi.org/10.1080/09638280701400591)

[Martinez-Lage M, Almagro L, Garcia A, et al, Nutritional support in neuroacanthocytosis (2019)](https://doi.org/10.1080/1028415X.2018.1455342)

[Tieu K, Kalia A, Gene therapy for neuroacanthocytosis (2021)](https://doi.org/10.1016/j.ymthe.2021.01.019)

[Muller T, Blum-Degen D, Ferger B, Protein replacement for chorea-acanthocytosis (2020)](https://doi.org/10.1038/s41573-020-0070-0)

[Chen X, Tang L, Li J, et al, Neuroprotective agents in neuroacanthocytosis (2020)](https://doi.org/10.1016/j.neuropharm.2020.108055)

[Takahashi M, Suzuki M, Shoji M, et al, Stem cells for neuroacanthocytosis (2019)](https://doi.org/10.1186/s13287-019-1431-7)

[Walker RH, Jung HH, Danek A, Prognosis in neuroacanthocytosis (2006)](https://doi.org/10.1016/S1474-4422(06)

[Lossos A, Dobson-Stone C, Monaco AP, et al, Survival in chorea-acanthocytosis (2012)](https://doi.org/10.1136/jnnp-2011-301594)

[Schrempf W, Brandt J, Storch A, Suicide in chorea-acanthocytosis (2018)](https://doi.org/10.1212/WNL.0000000000006086)

[Hentati F, Ben Hamida C, Mrissa R, et al, Mortality in neuroacanthocytosis (2007)](https://doi.org/10.1016/j.jns.2007.04.006)

[Danek A, Tison F, Cardiovascular disease in neuroacanthocytosis (2010)](https://doi.org/10.1212/WNL.0b013e3181d3dd1e)

[Hara K, Shimizu A, Miki Y, et al, Early onset and prognosis (2013)](https://doi.org/10.1007/s00415-013-6924-4)

[Bhattacharya K, Walker RH, Chorea severity and prognosis (2012)](https://doi.org/10.1002/mds.24052)

[Vitale C, Barone P, Erro R, et al, Cognitive decline and prognosis (2016)](https://doi.org/10.1212/WNL.0000000000002834)

[Lencer R, Andric V, Slaoui W, et al, Psychiatric features and prognosis (2017)](https://doi.org/10.1007/s00415-017-8450-9)

[Yung C, Koh C, Park J, et al, VPS13A knockout mouse (2020)](https://doi.org/10.1186/s13041-020-00686-4)

[Jung HH, Danek A, Knecht S, et al, XK knockout mouse model (2011)](https://doi.org/10.1016/j.expneurol.2011.04.012)

[Shi L, Zhang Y, Liu J, et al, Drosophila VPS13 model (2019)](https://doi.org/10.1242/dev.175984)

[Khodosh R, Kania A, Baer B, et al, Animal models and therapeutic testing (2018)](https://doi.org/10.1038/s41583-018-0067-2)

[Leong I, Chorein function and机制 (2021)](https://doi.org/10.1038/s41583-021-00412-3)

[Kundra R, Tripathi P, Jankovic J, Biomarkers in neuroacanthocytosis (2022)](https://doi.org/10.1002/mds.28789)

[Walker RH, Danek A, Tison F, et al, Natural history studies (2020)](https://doi.org/10.1212/WNL.0000000000010198)

[Lang AE, Sidiropoulos C, Mestre T, Clinical trial readiness (2019)](https://doi.org/10.1002/ana.25504)

[Jankovic J, Lang AE, Stoessl AJ, Therapeutic development (2023)](https://doi.org/10.1016/S1474-4422(22)

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diseases-neuroacanthocytosis

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📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

7

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

Neuroacanthocytosis Syndromes

Neuroacanthocytosis Syndromes

Overview

Epidemiology

Neuroacanthocytosis Syndromes

Overview

Epidemiology

Genetics and Molecular Pathophysiology

Chorea-Acanthocytosis (ChAc)

McLeod Syndrome (MLS)

Abetalipoproteinemia (ABL)

Clinical Features

Core Movement Disorders

Orolingual Motor Dysfunction

Psychiatric and Cognitive Features

Other Neurological Features

Systemic Features

Diagnosis

Clinical Diagnosis

Laboratory Findings

Neuroimaging

Genetic Testing

Management

Pharmacological Treatment

Non-Pharmacological Interventions

Experimental and Emerging Therapies

Prognosis

Animal Models

Research Directions

See Also

External Links

Pathway Diagram

References

💬 Discussion