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Mov Disord Clin Pract 2020 Apr 3;7(3):340-342. Epub 2020 Mar 3.

Department of Neurology Massachusetts General Hospital Boston Massachusetts USA.

Int J Mol Sci 2020 Mar 5;21(5). Epub 2020 Mar 5.

Section for Translational Neurodegeneration "Albrecht Kossel", Department of Neurology, Universitätsmedizin Rostock, 18057 Rostock, Germany.

Chorea acanthocytosis (ChAc), an ultra-rare devastating neurodegenerative disease, is caused by mutations in the gene, which encodes for the protein chorein. Affected patients suffer from chorea, orofacial dyskinesia, epilepsy, parkinsonism as well as peripheral neuropathy. Although medium spinal neurons of the striatum are mainly affected, other regions are impaired as well over the course of the disease. Read More

BMC Med Genet 2020 03 4;21(1):47. Epub 2020 Mar 4.

Research Team in Neurology and Neurogenetics, Genomics Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.

Background: Choreoacanthocytosis (ChAc), is a rare neurodegenerative disease, characterized by movement disorders and acanthocytosis in the peripheral blood smears, and various neurological, neuropsychiatric and neuromuscular signs. It is caused by mutations in VPS13A gene with autosomal recessive pattern of inheritance.

Case Presentation: Here we report two patients belonging to a consanguineous Moroccan family who present with movement disorder pathology. Read More

Mol Genet Genomic Med 2020 Feb 14:e1179. Epub 2020 Feb 14.

Neurologische Klinik und Poliklinik, Ludwigs-Maximilians Universität München, Munich, Germany.

Background: Chorea-acanthocytosis (ChAc; OMIM #200150) is a rare autosomal recessive condition with onset in early adulthood that is caused by mutations in the vacuolar protein sorting 13A (VPS13A) gene encoding chorein. Several diagnostic genomic DNA (gDNA) sequencing approaches are widely used. However, their limitations appear not to be acknowledged thoroughly enough. Read More

BMC Neurol 2019 Nov 27;19(1):301. Epub 2019 Nov 27.

Department of Neurology, Fukushima Medical University, Fukushima, Japan.

Background: McLeod syndrome is a rare X-linked recessive acanthocytosis associated with neurological manifestations including progressive chorea, cognitive impairment, psychiatric disturbances, seizures, and sensorimotor axonal polyneuropathy. However, no studies have investigated the functioning of central sensorimotor tracts in patients with McLeod syndrome.

Case Presentation: A 66-year-old man had experienced slowly progressive chorea and gait disturbance due to lower limb muscle weakness since his early fifties. Read More

J Neurol Sci 2020 01 31;408:116555. Epub 2019 Oct 31.

Department of Clinical Genetics, Helsinki University Hospital, Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

Tremor Other Hyperkinet Mov (N Y) 2019 21;9. Epub 2019 Aug 21.

Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, IN.

Background: Specific phenomenology and pattern of involvement in movement disorders point toward a probable clinical diagnosis. For example, forehead chorea usually suggests Huntington's disease; feeding dystonia suggests neuroacanthocytosis and risus sardonicus is commonly seen in Wilson's disease. Dystonic opisthotonus has been described as a characteristic feature of neurodegeneration with brain iron accumulation (NBIA) related to PANK2 and PLA2G6 mutations. Read More

Pediatr Neurol 2020 Feb 13;103:76-78. Epub 2019 Jun 13.

Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Tongue protrusion dystonia is an uncommon focal dystonia involving the lingual muscles. Causes of tongue protrusion dystonia include tardive dystonia, posthypoxic dystonia, neuroacanthocytosis, pantothenate kinase-associated neurodegeneration, and Lesch-Nyhan syndrome.

Method: We summarize three children with pantothenate kinase-associated neurodegeneration and tongue protrusion dystonia. Read More

Continuum (Minneap Minn) 2019 Aug;25(4):1001-1035

Purpose Of Review: This article provides an overview of the approach to chorea in clinical practice, beginning with a discussion of the phenomenologic features of chorea and how to differentiate it from other movement disorders. The diagnostic approach, clinical features of important acquired and genetic choreas, and therapeutic principles are also discussed. Practical clinical points and caveats are included. Read More

J Integr Neurosci 2019 06;18(2):197-201

Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 JingWu Road, 250021, Jinan, Shandong, P. R. China.

Neuroacanthocytosis is a rare progressive neurodegenerative disease, including Chorea-acanthocytosis, McLeod syndrome, Huntington's disease-like 2, and pantothenate kinase-associated neurodegeneration, where Chorea-acanthocytosis occupies the main entity of this disease group. Here, a classic case of Chorea-acanthocytosis is reported that exhibited gradually deteriorating abnormal movements of limbs and face, swallowing difficulty, and lip and cheek biting for the past two years. Peripheral blood smears revealed that 35% of the red blood cells were acanthocytes and electron microcopy scans clearly showed the morphology of acanthocytes. Read More

Parkinsonism Relat Disord 2019 07 2;64:293-299. Epub 2019 May 2.

Department of Neurology, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA; Department of Neurology, Mount Sinai School of Medicine, New York City, NY, USA.

Objective: To present five new McLeod Syndrome (MLS) pedigrees with novel XK gene mutations, review the literature of this disorder, and discuss the typical and atypical clinical features noted with these new mutations.

Methods: This is a multi-center retrospective review of five MLS cases with novel gene mutations. Genotypic and phenotypic information has been obtained from each center. Read More

Mov Disord Clin Pract 2018 May-Jun;5(3):333-336. Epub 2018 Apr 6.

Department of Neurology and Stroke Medicine Yokohama City University Graduate School of Medicine 3-9 Fukuura, Kanazawa-ku Yokohama, 236-0004 Japan.

Mov Disord Clin Pract 2018 Mar-Apr;5(2):223-224. Epub 2018 Feb 15.

Movement Disorder Division, Neurology Department New York University School of Medicine New York New York USA.

Elife 2019 02 11;8. Epub 2019 Feb 11.

Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

The gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. Read More

Parkinsonism Relat Disord 2019 05 10;62:248-250. Epub 2019 Jan 10.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Beijing TianTan Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Neurostimulation, Beijing, China. Electronic address:

Dis Model Mech 2019 01 28;12(1). Epub 2019 Jan 28.

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Department of Genetics, Pawinskiego 5A, 02106 Warsaw, Poland

Chorea-acanthocytosis (ChAc) is a rare neurodegenerative disease associated with mutations in the human gene. The mechanism of ChAc pathogenesis is unclear. A simple yeast model was used to investigate the function of the single yeast VSP13 orthologue, Vps13. Read More

Medicine (Baltimore) 2019 Jan;98(2):e14050

Department of Neurology, The First Hospital, Jilin University, Changchun, China.

Rationale: Neuroacanthocytosis (NA) is a heterogeneous group of inherited neurodegenerative disorders characterized by misshapen spiculated erythorcytes and symptoms that resemble Huntington's disease.

Patient Concerns: A 59-year-old female who developed hyperkinetic involuntary movements that became progressively more obvious during the course of a year.

Diagnoses: Acanthocytes were observed in a peripheral blood smear. Read More

Tremor Other Hyperkinet Mov (N Y) 2018 26;8:604. Epub 2018 Oct 26.

Department of Neurology, National Neuroscience Centre, Cork University Hospital, Cork, IE.

Rev Neurol (Paris) 2019 Jan - Feb;175(1-2):81-86. Epub 2018 Nov 5.

Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

Atypical motor neuron disease represents a rare heterogeneous group of neurodegenerative disorders with clinical, genetic and neuroimaging features distinct from those of the classic spinal or bulbar-onset amyotrophic lateral sclerosis (ALS). O'Sullivan-McLeod syndrome represents an extremely rare lower motor neuronopathy with early adult-onset distal amyotrophy and weakness in the upper limbs with asymmetrical involvement. To add to the few case series and epidemiological and genetic studies describing this variant syndrome, our team here presents a series of seven unrelated Brazilian patients with O'Sullivan-McLeod syndrome in a detailed review of their clinical, neuroimaging, laboratory and neurophysiological findings. Read More

Tremor Other Hyperkinet Mov (N Y) 2018 17;8:579. Epub 2018 Jul 17.

Parkinsonism Relat Disord 2019 03 14;60:158-161. Epub 2018 Sep 14.

Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.

Objective: To document life expectancy and causes of death in chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS).

Methods: We reviewed our personal databases and the published literature to identify cases of ChAc and MLS for whom adequate information was available regarding ages of disease onset and death, cause of death, and other clinical information.

Results: Adequate information was obtained on 52 patients with ChAc and 34 with MLS. Read More

Stereotact Funct Neurosurg 2018 28;96(4):276. Epub 2018 Aug 28.

Department of Neurosurgery, Jaslok Hospital and Research Centre, Mumbai, India.

JAMA Neurol 2018 12;75(12):1554-1562

Blood Transfusion Service Zurich, Swiss Red Cross, Schlieren/Zürich, Switzerland.

Importance: McLeod syndrome, encoded by the gene XK, is a rare and progressive disease that shares important similarities with Huntington disease but has widely varied neurologic, neuromuscular, and cardiologic manifestations. Patients with McLeod syndrome have a distinct hematologic presentation with specific transfusion requirements. Because of its X-linked location, loss of the XK gene or pathogenic variants in this gene are principally associated with the McLeod blood group phenotype in male patients. Read More

Mol Cell Neurosci 2018 10 3;92:137-148. Epub 2018 Aug 3.

Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany; Universitäts Centrum für seltene Erkrankungen, Technische Universität Dresden, Dresden, Germany. Electronic address:

Mutations in the VPS13A gene leading to depletion of chorein protein are causative for Chorea Acanthocytosis (ChAc), a rare devastating disease, which is characterized by neurodegeneration mainly affecting the basal ganglia as well as deformation of erythrocytes. Studies on patient blood samples highlighted a dysregulation of Actin cytoskeleton caused by downregulation of the PI3K pathway and hyper-activation of Lyn-kinase, but to what extent these mechanisms are present and relevant in the affected neurons remains elusive. We studied the effects of the absence of chorein protein on the morphology and trafficking of lysosomal and mitochondrial compartments in ChAc patient-specific induced pluripotent stem cell-derived medium spiny neurons (MSNs). Read More

Front Med (Lausanne) 2018 16;5:198. Epub 2018 Jul 16.

Department of Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.

The structure of red blood cells is affected by many inborn and acquired factors, but in most cases this does not seem to affect their function or survival in physiological conditions. Often, functional deficits become apparent only when they are subjected to biochemical or mechanical stress , or to pathological conditions . Our data on the misshapen red blood cells of patients with neuroacanthocytosis illustrate this general mechanism: an abnormal morphology is associated with an increase in the susceptibility of red blood cells to osmotic and mechanical stress, and alters their rheological properties. Read More

Biochem Biophys Res Commun 2018 09 21;503(2):915-920. Epub 2018 Jun 21.

Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60-61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Read More

Parkinsonism Relat Disord 2018 08 21;53:10-20. Epub 2018 May 21.

Department of Neuroscience and Behavior Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.

Diseases with a choreic phenotype can be due to a variety of genetic etiologies. As testing for Huntington's disease (HD) becomes more available in previously resource-limited regions, it is becoming apparent that there are patients in these areas with other rare genetic conditions which cause an HD-like phenotype. Documentation of the presence of these conditions is important in order to provide appropriate diagnostic and clinical care for these populations. Read More

Neuromodulation 2018 Dec 10;21(8):741-747. Epub 2018 Apr 10.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Introduction: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Read More

Chin Med Sci J 2018 Mar;33(1):53-59

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Chorea-acanthocytosis (ChAc) is the most common subtype of neuroacanthocytosis syndrome, characterized by the presence of acanthocytes and neurological disorders. It is thought to be caused by VPS13A mutations. Characteristic movement disorders in ChAc is choreiform movements affecting both trunk and extremities and prominent orolingual dyskinesia is pathognomonic. Read More

Clin Neurol Neurosurg 2018 05 1;168:64-66. Epub 2018 Mar 1.

Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, 69000 Lyon, France; Université de Lyon, CNRS, Institut des Sciences Cognitives Marc Jeannerod, UMR 5229, 69500 Bron, France; Université de Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon Sud Charles Mérieux, 69000 Lyon, France.

Neurol India 2018 Mar-Apr;66(Supplement):S157-S160

Department of General Medicine, District Hospital, Howrah, Kolkata, West Bengal, India.

Parkinsonism Relat Disord 2018 04 10;49:54-59. Epub 2018 Jan 10.

Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität München, Germany.

Introduction: Chorea-acanthocytosis (ChAc) and Huntington's disease (HD) are neurodegenerative conditions that share clinical and neuropathological features, despite their distinct genetic etiologies.

Methods: In order to compare these neuropathologies, serial gallocyanin-stained brain sections from three subjects with ChAc were analyzed and compared with our previous studies of eight HD cases, in addition to three hemispheres from two male controls.

Results: Astrogliosis was much greater in the ChAc striatum, as compared to that found in HD, with dramatic increase in total striatal glia numbers and the number of glia per striatal neuron. Read More

Parkinsonism Relat Disord 2018 04 20;49:17-21. Epub 2017 Dec 20.

Neurology Department, Hospital Ramón y Cajal, Madrid, Spain; Instituto Ramón y Cajal de Investigación IRICYS, Spain.

Eur J Med Genet 2018 Nov 16;61(11):699-705. Epub 2017 Dec 16.

Division for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany; DZNE, German Centre for Neurodegenerative Diseases, Research Site Dresden, 01307 Dresden, Germany. Electronic address:

Neuroacanthocytosis (NA) syndromes are a group of rare diseases characterized by neurological disorders and misshaped spiky red blood cells (acanthocytes) including Chorea-Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington disease-like 2 (HDL 2), pantothenate kinase-associated neurodegeneration (PKAN), abeta- and hypobetalipoproteinemia and aceruloplasminemia. This clinically and genetically heterogeneous group of diseases shares main clinical features presenting most often as a hyperkinetic movement disorder. Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms. Read More

Eur J Nucl Med Mol Imaging 2018 03 15;45(3):511-512. Epub 2017 Dec 15.

Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

Tremor Other Hyperkinet Mov (N Y) 2017 5;7:512. Epub 2017 Dec 5.

Division of Human Genetics, University of the Witwatersrand, Johannesburg, South Africa.

Background: Huntington's Disease-like 2 (HDL2) is classified as a neuroacanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington's disease (HD).

Methods: We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Read More

Rev Esp Med Nucl Imagen Mol 2018 Sep - Oct;37(5):328-329. Epub 2017 Dec 6.

Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, España.

Neurosignals 2017 28;25(1):117-126. Epub 2017 Nov 28.

Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.

Chorea-acanthocytosis (ChAc), a neurodegenerative disease, results from loss-of-function-mutations of the chorein-encoding gene VPS13A. Affected patients suffer from a progressive movement disorder including chorea, parkinsonism, dystonia, tongue protrusion, dysarthria, dysphagia, tongue and lip biting, gait impairment, progressive distal muscle wasting, weakness, epileptic seizures, cognitive impairment, and behavioral changes. Those pathologies may be paralleled by erythrocyte acanthocytosis. Read More

Orv Hetil 2017 Oct;158(42):1681-1684

Klinikai Központ, Orvosi Genetikai Intézet, Pécsi Tudományegyetem, Általános Orvostudományi Kar Pécs, József A. u. 7., 7623.

In a patient with marked symptoms of Huntington disease after the huntingtin testing, which gave normal result, a whole exome sequencing (WES) has been performed based on an international collaboration. A homozygous G>A nucleotid change in the exon 34 of the VPS13A gene has been detected with WES, a mutation resulting in a premature stop codon at the position 1301. This change is a known pathogenic mutation. Read More

Transfusion 2017 10;57(10):2307-2308

Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.

J Neurosurg Anesthesiol 2018 Oct;30(4):382-383

Department of Neuroanaesthesia and Neurocritical Care, National Institute of Mental Health and Neurosciences Bangalore, Karnataka, India.

Traffic 2017 11 24;18(11):711-719. Epub 2017 Sep 24.

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

Human Vps13 proteins are associated with several diseases, including the neurodegenerative disorder Chorea-acanthocytosis (ChAc), yet the biology of these proteins is still poorly understood. Studies in Saccharomyces cerevisiae, Dictyostelium discoideum, Tetrahymena thermophila and Drosophila melanogaster point to the involvement of Vps13 in cytoskeleton organization, vesicular trafficking, autophagy, phagocytosis, endocytosis, proteostasis, sporulation and mitochondrial functioning. Recent findings show that yeast Vps13 binds to phosphatidylinositol lipids via 4 different regions and functions at membrane contact sites, enlarging the list of Vps13 functions. Read More

Cell Physiol Biochem 2017 11;42(5):2066-2077. Epub 2017 Aug 11.

Department of Molecular Medicine II, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.

Background: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. Read More

Neurosci Lett 2017 Jul 20;654:107-110. Epub 2017 Jun 20.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University of Naples, Via S. Pansini, 5 IT-80131 Napoli, Italy.

Chorea-acanthocytosis (Ch-Ac) is an autosomal recessive neurodegenerative disorder characterized by adult-onset chorea, acanthocytes in the peripheral blood, and Huntington's disease-like neuropsychiatric symptoms. Animal studies have shown mutation-related dysregulated cortical gamma-aminobutyric acid (GABA)ergic inhibitory networks in its pathophysiology. Herein we found that in patients with Ch-Ac there is a striking alteration of intracortical inhibitory circuits detected by using paired pulse transcranial magnetic stimulation protocols. Read More

Fortschr Neurol Psychiatr 2017 May 23;85(5):270-273. Epub 2017 May 23.

Klinik für Neurologie, Heilig Geist-Krankenhaus, Köln.

Chorea-acanthocytosis is an uncommon neurodegenerative disorder. Early diagnosis is often challenging. The triad of orofacial dyskinesia, epileptic seizures, and hyperCKemia should alert neurologists of a neuroacanthocytosis syndrome. Read More

Transfusion 2017 09 28;57(9):2125-2135. Epub 2017 May 28.

Blood Transfusion Service Zürich, Swiss Red Cross (SRC), Zürich-Schlieren, Switzerland.

Background: McLeod syndrome (MLS) is hematologically defined by the absence of the red blood cell (RBC) antigen Kx on the transmembrane RBC protein, XK, representing a highly specific diagnostic marker. Direct molecular assessment of XK therefore represents a desirable diagnostic tool. Whereas pathogenic point mutations may be simply identified, partial and complete deletions of XK on Xp21. Read More

Parkinsonism Relat Disord 2017 08 17;41:124-126. Epub 2017 May 17.

Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.