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29 Nov 2014 Published by The Advocacy for Neuroacanthocytosis
Patients, Ginger and Glenn Irvine
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.
CLINICAL SIGNS
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
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 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
associate
:: naadvocacy.org
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
the website.
Stresa Symposium reveals significant insights for NA research by Ruth Walker
We are delighted to report some encouraging progress from NA researchers funded by the Advocacy, including vital new insights into the function of chorein, the coded protein of the chorea-acanthocytosis (ChAc) gene VPS13A first discovered 13 years ago. The developments were reported at News Frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside.
Taking place on 30 October to 1 November 2014 at Stresa, on the shores of Lake Maggiore, Italy, the meeting was our third joint symposium and was organized by Lucia DeFranceschi (University of Verona), Sonia Levi (Vita-Salute San Raffaele University, and the San Raffaele Scientific Institute, Milan), and Valeria Tiranti (IRCCS Foundation Neurological Institute “C. Besta”, Milan). This meeting continues to expand upon the formal collaboration between researchers studying these two groups of very rare neurodegenerative disorders which was developed at the first joint meeting in Bethesda in 2010.
The meeting brought together an international group of clinicians and basic scientists from a wide variety of disciplines, and was attended by over 120 participants. Patient group representatives, family members, and affected patients from around the world also met in parallel and participated in a joint session.
The meeting was generously supported by the International Parkinson Disease and Movement Disorders Society, in addition to the Advocacy for Neuroacanthocytosis Patients, AISNAF, AOUI-Verona, ApoPharma Inc., AISNAF, Emina-Two, European Science Foundation, the European Union, Instituto Neurologico Carlo Besta, NBIA Alliance, Ospedale San Raffaele, Proteostasis, Retrophin, Sistema Sanitario Regio Lombardia, TIRCON, Universita degli Studi di Verona, Universita Vita-Salute San Raffaele.
Significant progress has been made since the last joint meeting in 2012. The TIRCON project, the first double-blind, controlled, study in PKAN, is underway and very successfully recruiting patients. There are other promising compounds for NBIA disorders in the pipeline. New molecular techniques such as whole exome sequencing have led to the identification of new NBIA genes, and to expansion of the clinical phenotype of previously-identified genes. Work continues in the study of the effects of mutations affected genes in a number of model systems, including iPS cells, yeast, and drosophila.
Importantly, 13 years after the discovery of the chorea-acanthocytosis (ChAc) gene VPS13A, the first substantial insights into the function of chorein, its coded protein, were presented, utilizing disease models in Drosophila, yeast, the slime mould dictyostelium, and human induced pluripotent stem cells. Studies were presented of ion transport dysfunction in erythrocytes in the even rarer McLeod syndrome. Two other members of the VPS13 gene family were discussed; VPS13B, which is responsible for Cohen syndrome, and VPS13C, which was recently linked to frontotemporal dementia, thus suggesting a potential link with neurodegenerative processes.
The significance of acanthocytosis in PKAN, in addition to other NA syndromes, remains poorly understood. As the patient groups for the various NBIA syndromes become increasingly organized, the connection between the two groups of disorders may soon be re-investigated with systematic exploration of blood smears for acanthocytes. Plans are under way to continue this fruitful collaboration, which has benefited both the NBIA and the NA fields, at a meeting in 2016, most likely in North America.
Three early-career investigators were awarded scholarships to attend, to foster collaboration with more senior scientists in the field, and to support their continued contributions to the field.
We will continue to report further developments from our researchers in future issues of NA News.
