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
What do spiky red blood cells have to do with neurodegeneration? After 10 years, NA researchers have refined their working hypothesis on acanthocytosis in NA patients. Using insights gained at the London/Oxford symposium in 2008, the hypothesis has been refined to: “The anomalies in the red blood cells causing acanthocytosis relate to a malfunction in the membrane that in neurons may hamper normal autophagy and lead to cell death.”
Prof Giel Bosman and Prof Lucia de Franceschii
The work of Prof Lucia de Franceschi at the University of Verona and Prof Giel Bosman at the University Nijmegen Medical Centre has just been published in the internationally- recognised journal “Blood” (see doi:10.1182/blood-2011-05-355339): Erythrocyte membrane changes of chorea-acanthocytosis are the result of altered Lyn kinase activity.
In May 2002 the First Symposium on Neuroacanthocytosis heard the speculation that functional anomalies in band 3 of cell membranes may be involved in generation of acanthocytes. The earliest research commissioned by the Advocacy began the exploration of the cause. The first step was a small project conducted through Mount Sinai Medical Center in New York where Ruth Walker is Associate Professor.
With the financial support of Carl and Betty Pforzheimer, blood samples of patients were analysed by Prof Bosman at the University Nijmegen Medical Centre, Nijmegen, The Netherlands. Prof. Bosman’s work continued in collaboration with Prof de Franceschi at the University of Verona, Italy. This work received support from foundations of the Leonard Blavatnik Family in 2008. The investigation was incorporated into the European Multidisciplinary Investigation into Neuroacanthocytosis (EMINA).
Profs de Franceschi and Bosman report that the significance of their investigation is a novel mechanism for generation of acanthocytes in ChAc.
Using an integrated proteomic approach, the researchers found 'instability' of band 3 junctional complexes bridging the membrane to the cytoskeleton of ChAc red cells. The research found increased tyrosine-phosphorylation of band 3 together with several membrane proteins leading to altered linkage of band 3 to the junctional complexes in ChAc red cells. The researchers then looked at the signalling pathway towards band 3 and found abnormal activation of Lyn, a kinase from the Src family, independently of the canonical Syk-mediated pathway described in red cells from healthy donors. Future studies are planned to study the Lyn-related signalling cascade in ChAc red cells and in other NA disorders by integrated and functional proteomic approaches.
Lyn and Syk as tyrosine kinases belong to the larger class of protein kinases which attach phosphate groups to other amino acids. They function as "on" or "off" switches in many cellular functions". Phosphorylation of proteins by kinases is an important mechanism in communicating signals within a cell and regulating activity of cells such as circulating red blood cells or stationary nerve cells.