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
Winning grant applications announced by the Advocacy A tremendous response was received to the Advocacy's call for research applications at the end of 2011.
After review by our independent scientific panel, two of the seven research grant applications were approved and have been confirmed to the researchers below.
Please note that the third project below, funded by the family of Mark Williford, may offer a chance for patients and their families, and for their physicians, to get involved:
Aaron Neiman, Stony Brook University, New York
Vps13a regulation of phosphatidylinositolphosphate pools in mammalian cell
The genetic disease chorea acanthocytosis is caused by mutations in the gene VPS13A in humans. VPS13A encodes an evolutionary conserved protein of unknown molecular function. We have found that during the development of spores in the baker's yeast, Saccharomyces cerevisiae, the yeast homolog of VPS13A regulates the growth of intracellular membranes by controlling the levels of specific membrane components termed phosphatidylinositol phosphates. We will examine if the mammalian protein similarly regulates phosphatidylinositol phosphates. These membrane components are involved in a variety of cellular functions. Alteration of these components in cells lacking VPS13A could account for the symptoms of chorea acanthocytosis and suggest avenues for treatment of the disease
Florian Wegner, Alexander Storch, Andreas Hermann, Dresden Technical University
Functional analyses of ion channels in chorea-acanthocytosis
The aim of this research project is to gain insight into the functional pathomechanisms of chorea-acanthocytosis (ChAc), an autosomal-recessive neurodegenerative disease of young adults manifesting in a hyperkinetic movement disorder and other severe neurological symptoms as well as in misshaped red blood cells. This disease is caused by mutations in the VPS13A gene leading to a loss of the largely unknown function of the protein Chorein. Recently, we established a human in vitro model of ChAc using reprogrammed skin fibroblasts from ChAc patients. The genetic transformation of easily accessible patient cells allowed the generation of disease-specific induced pluripotent stem cells (iPSC) that behave similarly to embryonic stem cells without raising ethical concerns. iPSC-derived neurons are indeed believed to be the best human cell model for neurological diseases.
In this project, the ChAc patient-derived iPSC will be differentiated into various types of neurons to study their ion channel function and synaptic activity by electrophysiological and calcium-imaging methods. Particularly, the analysis of synaptic activity in disease-specific neurons is of great interest because we recently identified severe actin-related cell membrane disturbances in erythrocytes from ChAc patients. This impairment of the cell membrane function may result in pathological synaptic currents due to the presynaptic role of the ChAc actin in neurons. We will compare the functional data of disease-specific neurons with neuronal cells derived from healthy controls in order to shed light on the functional pathophysiology and identify a potential therapeutic target to treat ChAc.
Alicia Rivera PhD at Children’s Hospital, Harvard Medical School, Boston
Separately the family of Mark Williford, supported by the Advocacy, has made a grant to Alicia Rivera PhD at Children’s Hospital, Harvard Medical School, Boston in her study of “The role of XK protein in Erythrocyte ion transport function”.
Alicia is currently recruiting adults with McLeod syndrome for a research project at Children’s Hospital Boston/Harvard Medical School, who are not taking any medications. Children’s Hospital Boston (USA) is an academic medical center, dedicated to excellence in both patient care and research.
To NA patients and their families: you may qualify to help with this research study:
If you have been told by your doctor that you have McLeod syndrome, or that you lack the Kx antigen in your red cells, you may qualify for this research study. It is important that you are not taking any medication as this could interfere with the studies of red cells. We are only approved to recruit adults over the age of 21 years.
This study will test the molecular mechanisms that are important in the development of acanthocytic red cells. If you qualify, participation would involve 2 visits to your doctor to give a medical and family history and to have blood samples taken. There are no medications involved. As part of the study you will be asked to contact close family members to see if they would also like to participate. You will not receive any personal health benefits as a result of your participation in this research study. However, the results will allow us to better comprehend McLeod syndrome and thus benefit patients in the future.
For physicians with NA patients in their care:
We are seeking patients who have been diagnosed with lack of Kx antigen, McLeod syndrome. No medication for neurological, or other disorders such as benzodiazepines, anticonvulsants, anti-hypertensive or other cardiac medications, and antidepressants.
There are no medications involved. Researchers will isolate DNA from one blood sample, so that they can confirm the lack of Kx antigen. The study will assess cation transport across intact red blood cells and estimate how this critical red cell function is affected by the absence of XK protein.
If you would like to receive additional information about participating in this important Institutional Review Board approved research study, please contact Dr. Alicia Rivera, Principal Investigator, or Dr. Ruth Walker, patient recruiter by email: email@example.com or firstname.lastname@example.org.