Cover Page»
:: 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.

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.
  • Search Google for the latest on NA
  • 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.

  • Patients' Centre
  • Clinic
  • Library
  • Symposia
  • NA News
  • Research
  • Fundraising


:: Previous Issues
NA News Issue 15

NA News Issue 14

NA News Issue 13
:: Join NA News

NA News

Email Address:
Remove

RESEARCH UPDATE
European Multidisciplinary Initiative on Neuroacanthocytosis Interim Report

François Tison and colleagues in Bordeaux
François Tison and colleagues in Bordeaux
Interim reports from the European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA) have now been published. EMINA marks the first time NA research has attracted significant European Union investment of €650,000, and following the most recent EMINA progress meeting in Bordeaux in October, full updates from a number of investigators are now available on the NA Advocacy website, including the following:

François Tison, Marie Chauveau, Umberto Spampinato, Chrystelle Latxague
“Clinical evaluation of patients with Neuroacanthocytosis”, aimed at creating taxonomy, diagnosis and treatment guidelines for the Neuroacanthocytosis (NA). It includes two main protocols:
a) Retrospective data analysis from patients with Neuroacanthocytosis and Deep Brain Stimulation (NASCeP);
b) Analysis of movement disorders in patients suffering from Neuroacanthocytosis: design and validation of a clinical rating scale based on video tape evaluation (NAcEVi).


Claudia Roos, Patricia Hamminger, Manuel Nustes, Ulrich Salzer, Rainer Prohaska
The Medical University of Vienna (MUV) project entitled “Erythrocyte membrane domains in neuroacanthocytosis” is aimed at the microscopic and biochemical analysis of acanthocyte membrane domains. The respective data may shed light on the pathomechanism of the neuronal defect.

Giel Bosman, Judith Cluitmans
The Radboud University Medical Center in Nijmegen (RUN) project “Vesicle formation in neuroacanthocytosis”, started with the development of an erythrocyte model for acanthocytosis. The approach is inspired by recent proteomic and immunochemical data indicating that specific disruption of the binding of the lipid bilayer to the cytoskeleton underlies both the acanthocyte cell shape and disturbed vesicle generation.

Jan J. Vonk, Cecile Deelman-Driesen, Ody C. M Sibon – University Medical Center Groningen (UMCG) project
Neuroacanthocytosis patients have a striking combinational phenotype of neurodegeneration in the brain and the presence of acanthocytes in their blood. The goal of this project is to establish Drosophila melanogaster models for Chorea-acanthocytosis (ChAc) and Huntington’s disease-like 2 (HDL2) and compare these, together with the already established Drosophila model of PKAN, to find a common underlying pathological mechanism shared by NA syndromes.


Additional research supported the Advocacy for Neuroacanthocytosis Patients - Autumn 2011 update

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

The overall aim of our ongoing project is to establish an in vitro model of ChAc using nerve and blood cells from reprogrammed fibroblasts (human induced pluripotent stem cells; hiPS) 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.

We recently identified several secondary cell membrane disturbances within erythrocytes from ChAc patients. Interestingly, this is obvious neither in neurons derived from ChAc-hiPS nor in fibroblast cells suggesting different downstream targets of VPS13A gene in different cell types. However, it could be also a hint towards neuronal subtype specific vulnerability.

Thus, after having established a general neuronal differentiation of ChAc-hiPS lines, the last six months were used to develop and optimise differentiation protocols for high yield of erythrocytes as well as striatal nerve cells (medium spiny neurons) from ChAc-hiPS. This will enable us to investigate the major neuronal cell type lost in ChAc (namely medium spiny neurons).

This is of central interest since the results mentioned above from fibroblasts, erythrocytes and non-striatal nerve cells point towards an organ or neuronal subtype specific pathophysiological role and thus therapeutic target of ChAc. We recently proved the importance of the development of a human ChAc cell model, which is now optimised for cell type specific differentiation.

Thus we now have the cells of interest in hand to start screening for the role of neuronal as well as erythrocytes pathophysiology, and thus to reach the overall aim of developing a sufficient causal therapy for this disease.


Purification and biochemical function of yeast Vps13 protein
Robert S. Fuller, Ph.D. and Mithu De, Ph.D.   

Department of Biological Chemistry University of Michigan Medical School

This grant was awarded in August 2010, to support studies by postdoctoral fellow Mithu De on the basic biochemistry of Vps13 protein (Vps13p), the yeast homolog of the Chorea Acanthocytosis disease protein, chorein. The yeast VPS13/SOI1 gene was identified by mutations that blocked the cycling of the Vps10p vacuolar protein sorting receptor and the proprotein processing protease, Kex2, between the yeast Golgi and late endosome.

Previously, genetic experiments indicated that Vps13p is required for retrograde vesicular trafficking from the late endosome to the Golgi and suggested that it played a role in trafficking at the TGN. Our results now show that Vps13 is directly required for forward transport from the TGN to the late endosome. We have shown by reconstituting TGN-late endosome vesicular transport in a cell-free system. Extracts from vps13 null and conditional mutants are defective for transport but transport is rescued by adding Vps13p protein purified from yeast.

We have shown as well that transport requires the small calcium binding protein, Cdc31/Centrin, and that extracts from a conditional cdc31 mutant, which are defective for transport, can be rescued by the purified Vps13p fractions. Vps13p is a peripheral membrane protein that associates with the late endosome.

In order to study the mechanism of recruitment of Vps13p to membranes, we have established a membrane-binding assay and shown that purified Vps13p binds to membranes in an ATP-dependent fashion. Deletion analysis is being used to identify domains of Vps13p required for membrane association and binding of Cdc31/Centrin.

Share | 0 Comments | Post a Comment