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
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 www.naadvocacy.org
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
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 amazon.com
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.
Visit the NA page on WeMove,
the Movement Disorder Societies charitable and educational
naadvocacy.org 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
RESEARCH UPDATE Analysis of Lyn pathway in target cells from chorea-acanthocytosis and development of new chorea-acanthocytosis mouse model Dr. Lucia de Franceschi in Verona University of Verona, Italy
Dr. Lucia de Franceschi in Verona has received a research grant from the Advocacy for her project. This work will also include collaboration to compare the observations she has made in studying red blood cells from ChAc patients with the findings of Florian Lang, Andreas Hermann, Alexander Storch and eventually Florian Wegner, whose investigations focus on the iP stem cells generated from the skin of ChAc patients. The project will also help in generating the synergy to progress in the knowledge of ChAc.
Functional Characterisation of chorein Dr. Antonio Velayos-Baeza Wellcome Trust Centre for Human Genetics, University of Oxford, UK
Our research on ChAc is focussed on the functional characterisation of chorein. One aspect involved in this project is to analyse the effect on chorein properties of particular pathogenic mutations (changes found in patients affected with ChAc) which only introduce minimal changes in the sequence of the VPS13A protein, such a single amino acid substitutions or the loss or addition of a short stretch of residues. In these cases it is not predicted that the mutated protein is lost, but it is possible that its stability, localisation, or particular functions are affected. When available, samples from ChAc patient(s) with these mutations are analysed to check if the protein is detected at normal levels. Furthermore, these changes are introduced in the coding sequence of the VPS13A gene on an expression vector which is then used for transfection of mammalian cell lines. We are generating several of these constructs and collecting some samples from ChAc patients to do these analyses. We are also addressing some remaining questions about the causing mutations in some ChAc patients, in particular the characterisation of several large deletions, and collaborating in several on-going projects on different aspects of ChAc.
Investigation on membrane alterations in NA erythrocytes Claudia Siegl, Rainer Prohaska and Ulrich Salzer Max F. Perutz Laboratories, Medical University of Vienna, Austria
Acanthocytosis, the occurrence of thorny-shaped red cells, is a diagnostic feature associated with NA syndromes. Whereas acanthocytes are frequently present in the blood of ChAc and MLS patients, acanthocytosis is observed only in about 10% of the NBIA patients. Our study aims at identifying functional similarities and differences between erythrocytes of the NA syndromes in order to better understand molecular processes associated with the formation of acanthocytes. Therefore, we established a biochemical assays to test the flexibility of the plasma membrane and the ability to form endovesicles. Further assays assessed the tendencies for phosphatidylserine exposure und uptake of calcium in response to a specific stimulating drug. We find that erythrocytes from NA patients show a significantly impaired response in these assays, however, only when acanthocytes are present. This indicates that acanthocytosis is only one of several interdependent aberrations of the erythrocyte plasma membrane that commonly occur in erythrocytes from NA patients. These results are currently being submitted for publication. At the moment it is neither known whether there is a common cause underlying these aberrations nor why this “acanthocytic state” is frequent in ChAc but rare in NBIA. Ongoing studies aim at answering these questions and thereby may provide clues for aberrant molecular processes that also occur in neurons and hence be associated with neurodegeneration.
Functional analyses of ion channels in Chorea-Acanthocytosis (ChAc) patient-derived induced pluripotent stem cells and differentiated neurons in vitro. PD Dr. med. Florian Wegner, Department of Neurology Hannover Medical School, Germany
The aim of our project is the functional characterization of induced pluripotent stem cells (iPSCs) and differentiated neurons derived from Chorea-Acanthocytosis (ChAc) patients to gain insight into the pathophysiology of this devastating neurodegenerative disease. We successfully differentiated iPSCs from ChAc patients and a healthy control into neuronal cells to study their synaptic activity, ion channel and action potential properties using whole-cell patch clamp recordings and calcium imaging. The first functional data are pointing to altered sodium and potassium channel amplitudes as well as synaptic activity in neurons from ChAc patients compared to healthy controls. Particularly the voltage-gated sodium channels are important for the generation and conductance of action potentials in neurons. A pathological excitability of ChAc neurons may be linked to clinical symptoms like hyperkinesia and epileptic seizures and could represent a relevant therapeutic target to treat ChAc.
Vps13a regulation of phosphatidylinositolphosphate pools in mammalian cell Aaron Neiman, Stony Brook University, New York
Understanding the molecular function of the chorein protein is essential for the development of treatments for chorea-acanthocytosis. We have discovered a role for the yeast version of chorein, Vps13, in regulation of specific lipids during the process of sporulation. With funding from the Advocacy, we have tested if chorein has a related function in mammalian cells. Using genetic techniques to lower the level of chorein in cultured cells, we observed similar effects on lipid pools to those found in yeast cells deleted for VPS13. These results indicate that lipid regulation is a conserved function of the Vps13 family proteins and suggest a possible molecular basis for some of the symptoms of chorea-acanthocytosis.