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:: How to recognise Neurocanthocytosis

The first signs of the diseases in the neuroacanthocytosis (NA) group are subtle and easily overlooked. Initial symptoms, which often occur in the person’s mid 20’s, may include grunts or tic noises made unconsciously in the throat, progressing to drooling and problems in controlling the tongue from ejecting food. Involuntary biting of the tongue, lips and/or cheeks may follow.

At the beginning there can be a general, slight physical awkwardness. Things on a shelf are knocked off for no apparent reason. Difficulty with walking and balance can also be early symptoms. Problems controlling trunk, leg and arm movements are often barely noticeable at the beginning, but become increasingly difficult as the disease progresses. Several patients find it difficult to sleep at night and others report fatigue and weakness.

Personality change may also be an early indication. The carefree young adult becomes obsessive-compulsive and uncharacteristically forgetful or just loses confidence or drive. Fainting or epileptic seizures may also occur. Mood changes may happen and a person often becomes isolated, in part out of embarrassment.

There are several reports of the problems beginning after a traumatic event including physical attack, unexpected failure of an exam and birth of a child.


A defining symptom that is not apparent is the spiky red blood cells, or acanthocytes, from which the NA disease group takes its name. These unusual blood cells can be observed with a microscope in some circumstances. Still more difficult to observe are the alterations or mutations in patients’ genes. Each of the NA group diseases has a different genetic characteristic that can be determined only by blood tests.

A person showing some of this pattern of symptoms should see a neurologist. Clinicians and patients can also visit for links to further scientific reports. Full details are also available on the free blood testing service offered by the Advocacy for Neuroacanthocytosis Patients, aimed at helping determine a definitive diagnosis for NA.

:: Useful NA Resources

  • Neuroacanthocytosis Syndromes II, published December 2007, the book provides a profound insight into recent developments within the field of neuroacanthocytosis syndromes. Edited by Ruth H. Walker, Shinji Saiki and Adrian Danek. Available at
  • A Western blot test for the presence of chorein in the membranes of red blood cells can be offered free of charge due to support of the Advocacy for Neuroacanthocytosis Patients'. Download instructions on the blood sampling and specimen shipment as a PDF or get more information on the method at PubMed
  • The entry for chorea acanthocytosis in GeneReviews is the most complete, readily available report on ChAc. Published by the University of Washington with the support of the National Institutes of Health
  • A dedicated Patient & Families Support Group at Yahoo Groups offers patients and families information, advice, support or just an understanding ear
  • Visit PubMed for access to NA research in English from the Medline database.
  • Search Google for the latest on NA
  • Visit the NA page on WeMove, the Movement Disorder Societies charitable and educational associate

:: is the website of the The Institute for Neuroacanthocytosis. It is the Advocacy's international centre for supporting patients and promoting clinical and basic research. The website provides access to resources found on the website.

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Research Update
Neuroacanthocytosis research in Nijmegen: from biochemistry to cell biology and beyond
Dr. Giel Bosman
Department of Biochemistry
Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular
Life Sciences:


In our 2007 project “A proteomic inventory of the erythrocytes (red blood cells) of patients with neuroacanthocytosis”  we aimed to identify the molecular lesion(s)causing acanthocyte formation, using recently developed techniques in the fields of proteomics and bioinformatics.

In the first part of this project we developed specific methodology for qualitative and quantitative analysis of the protein composition of the erythrocyte membrane. The resulting methods are widely applicable; for example, they are now also used in research on the cause of hemolytic anemia in children with malaria (Bosman et al, in preparation). Using these methods, and in close collaboration with neurologists and hematologists in the NA network, we have generated a reliable, comprehensive inventory of the erythrocyte membrane proteome of the three major forms of NA.

This inventory pinpoints two NA form-related lesions in the anchorage sites of the cytoskeleton with the membrane. This not only confirms previous data (reported during the Oxford and Kyoto meetings) but, more importantly, it inspired new theories on the mechanisms of acanthocyte formation. One of these theories on a NA-associated disturbance of protein-protein interactions, is supported by the data from a parallel project on signaling in NA erythrocytes (Bosman and De Franceschi, in preparation). At another level, we hypothesize that altered cytoskeleton-membrane
interactions affect vesicle formation.

Cell biology

In our current research, supported by the European Community (EMINA program) and the Advocacy for Neuroacanthocytosis Patients, and in close collaboration with fundamental and clinical research groups, we aim to translate the proteomic data to the cell biology of acanthocyte formation. More specifically, we are investigating NA-related alterations in signal transduction pathways and vesicle formation. One major aim of this project is the development of a cellular acanthocytosis model in vitro, using a combination of biochemical, immunochemical, and state-of-the-art microscopy techniques.

Such a model will not only be instrumental in exposing pathological mechanisms, but also be the cornerstone of a high-throughput screening system for drug discovery. The latter will be of great importance for further fundamental and clinical studies, and thereby constitute the translation of our fundamental research into a therapy.


In parallel and/or future projects, the proteomic and cell biological knowledge obtained from erythrocyte studies will be used for in-depth studies on differentiating erythropoietic (maturing red blood) cells and neurons. This will culminate in the development of an informative neuronal and/or animal model of NA neurodegeneration. Application of stem cell technology seems an efficient approach to reach this goal. Therefore, an overview of current stem cell theory and practice would be useful in the next NA meeting.

Towards an understanding of the biochemical and cellular functions of VPS13 proteins
Robert S. Fuller, Ph.D. and Mithu De, Ph.D.
Department of Biological Chemistry
University of Michigan Medical School

Chorea-acanthocytosis is caused by mutations that inactivate the human VPS13A gene. We know that loss of the function of the VPS13A gene product results in the eventual death of striatal neurons of the basal ganglia and defects in red blood cells (acanthocytosis). A straight forward hypothesis is that VPS13A is required for a cellular process that is critical both for neuronal survival and for normal red blood cell structure. We do not know what that process is, but identifying it is essential both to understanding why the neurons die and to devising possible therapeutic strategies. The approach we are taking is to study the function of an evolutionarily related gene in a model microbe, baker's yeast (Saccharomyces cerevisiae).

The name of the VPS13A gene comes from a gene in baker's yeast, VPS13, which was discovered based on its role in the selective transport of proteins between two membrane-enclosed organelles in the yeast cell termed the trans Golgi network (TGN) and the late endosome (LE). This TGN-LE pathway is essential for the maintenance of the yeast lysosome or vacuole, another membrane enclosed organelle. The lysosome acts as a kind of cellular garbage disposal, digesting cellular components such as proteins and lipids. The TGN-LE pathway is also needed to maintain the function of yet another membrane-enclosed organelle, the Golgi complex, which is required for the correctly modifying proteins that are secreted or released from cells. Mutations in the yeast VPS13 gene block the TGN- LE pathway, interfering with normal lysosome and Golgi complex function.

Our laboratory originally isolated the yeast VPS13 gene in 1997 and identified the product of the gene, Vps13p, a novel and unusually large protein. We have now developed a method for reconstituting in the test tube protein -trafficking between the TGN and LE using extracts of yeast cells. This assay has allowed us to measure the biochemical activity of the Vps13 protein, to show that it functions directly in TGN-to-LE trafficking and to purify the active form of the protein. Analysis of the purified protein and other proteins that associate with the active protein will give us critical information about how the Vps13 family of proteins function in cells and what molecules they communicate with. This information will allow us to formulate testable hypotheses about how VPS13A functions in human cells.

This work has been supported by a grant from the NIH (GM50915) and generous support from the Advocacy for Neuroacanthocytosis Patients.

In vitro modelling of Chorea-acanthocytosis (ChAc): Patient fibroblasts and
their reprogrammed derivatives as human models of ChAc
Prof Alexander Storch
Department of Neurology
Dresden Technical University

The overall aim of our ongoing project is to establish an in vitro model of ChAc using skin fibroblast lines and reprogrammed fibroblasts (induced pluripotent stem (iPS) cells) from patients suffering from ChAc. Both cell types will be used as in vitro models to study basic mechanisms of the molecular pathophysiology of ChAc. In the first months of the funded project we succeeded to derive IPS cell lines from two patients. Having just proved the disease genotype in these samples, we will investigate the molecular pathophysiology and the molecular differences within striatal vs. other neuronal subtypes. Already we identified severe cytoskeleton disturbances within erythrocytes from ChAc patients. Interestingly, these differences are not evident in the neurons derived from ChAc-hiPS neurons. This suggests that the VPS13A gene has different functions in different cell types from the same patient.

The importance of an organ-specific pathophysiological role and therapeutic targeting of ChAc is of central interest for further drug development. Thus, we could prove the value of the development of a human ChAc cell model, which now needs to be scaled up to reach the overall aim of developing a sufficient causal therapy for this disease.

Research Project reports: Diagnostic Testing
Benedikt Bader

Munich has provided free tests for 300 patients that have helped with a positive diagnosis in 100 cases in 33 countries: Argentina, Australia, Austria, Brazil, Canada, Czech Republic, Chile, China, Finland, France, Germany, Greece, Hungary, India, Iran, Ireland, Israel, Italy, Malaysia, Norway, Korea, La Reunion, Poland, Portugal, Puerto Rico, Switzerland, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom and the United States.

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