Acanthocytosis

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Adrian Danek - One of the best experts on this subject based on the ideXlab platform.

  • Neurofilament light chain in serum is significantly increased in chorea-Acanthocytosis.
    Parkinsonism & Related Disorders, 2020
    Co-Authors: Kevin Peikert, Adrian Danek, Katja Akgün, Christian Beste, Tjalf Ziemssen, Carsten Buhmann, Andreas Hermann
    Abstract:

    Abstract Introduction Chorea-Acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease, characterized by hyper- and hypokinetic movement disorders, peripheral neuropathy and Acanthocytosis. Biomarkers are not established; possible candidates include neurofilament reflecting neuroaxonal damage. Methods We studied serum neurofilament light chain (sNfL) of six ChAc patients compared to two healthy control cohorts (A, six age/sex matched and B, historical cohort of 59 healthy adult subjects) and in two patients with the very similar condition of McLeod syndrome (MLS), the second core syndrome of neuroAcanthocytosis. sNfL was quantified using single-molecule array analysis. Results sNfL concentration was significantly higher in the ChAc cohort (18.73 pg/ml; IQR 15.65–27.70) compared to both healthy control cohorts (A, 7.37 pg/ml; IQR 5.60–9.05; B, 3.10 pg/ml; IQR 2.43–3.98). In MLS patients, a similar sNfL increase was observed. Conclusions sNfL is significantly increased in ChAc and MLS and seems to reflect neuroaxonal damage in the peripheral as well as the central nervous system.

  • hippocampal sclerosis and mesial temporal lobe epilepsy in chorea Acanthocytosis a case with clinical pathologic and genetic evaluation
    Neuropathology and Applied Neurobiology, 2017
    Co-Authors: Karin Mente, Adrian Danek, Christopher Grunseich, Marco M Hefti, John F Crary, Barbara I Karp, Ruth H. Walker
    Abstract:

    Chorea-Acanthocytosis (ChAc) is an autosomal recessive neurodegenerative disease associated with mutations in VPS13A that encodes the protein chorein. ChAc is characterized by progressive chorea, dystonia, and psychiatric symptoms, developing in young adulthood, often with Acanthocytosis in peripheral blood. Tongue protrusion, or feeding dystonia, is common, as are seizures and neuropathy [1]. On neuropathology, there is basal ganglia atrophy, neuronal loss, and gliosis, especially in the caudate nucleus [2]. We report the case of a patient with ChAc with hippocampal sclerosis who had extensive longitudinal follow-up, including neuropathology and general autopsy. This article is protected by copyright. All rights reserved.

  • Early Diagnosis of Chorea-Acanthocytosis: Orofacial Dyskinesia, Epileptic Seizures, and HyperCKemia
    Fortschritte der Neurologie-Psychiatrie, 2017
    Co-Authors: Christian Schneider, Adrian Danek, Arwed Hostmann, Gereon R Fink, Lothar Burghaus
    Abstract:

    Chorea-Acanthocytosis is an uncommon neurodegenerative disorder. Early diagnosis is often challenging. The triad of orofacial dyskinesia, epileptic seizures, and hyperCKemia should alert neurologists of a neuroAcanthocytosis syndrome. The diagnosis can be confirmed by detection of chorein deficiency or through molecular genetics (VPS13A mutation).

  • eighth international chorea Acanthocytosis symposium summary of workshop discussion and action points
    Tremor and other hyperkinetic movements (New York N.Y.), 2017
    Co-Authors: Samuel S Pappas, Adrian Danek, Lucia De Franceschi, Juan S Bonifacino, William T Dauer, Mithu De, Gilbert Dipaolo, Robert S Fuller, Volker Haucke, Andreas Hermann
    Abstract:

    Chorea-Acanthocytosis (ChAc) is a rare hereditary neurological disorder characterized by abnormal movements, red blood cell pathology, and progressive neurodegeneration. Little is understood of the pathogenesis of ChAc and related disorders (collectively NeuroAcanthocytosis). The Eighth International Chorea-Acanthocytosis Symposium was held in May 2016 in Ann Arbor, MI, USA, and focused on molecular mechanisms driving ChAc pathophysiology. Accompanying the meeting, members of the neuroAcanthocytosis research community and other invited scientists met in a workshop to discuss the current understanding and next steps needed to better understand ChAc pathogenesis. These discussions identified several broad and critical needs for advancing ChAc research and patient care, and led to the definition of 18 specific action points related to functional and molecular studies, animal models, and clinical research. These action points, described below, represent tractable research goals to pursue for the next several years.

  • Alterations of Red Cell Membrane Properties in
    2016
    Co-Authors: Claudia Siegl, Benedikt Bader, Adrian Danek, Patricia Hamminger, Herbert Jank, Uwe Ahting, Allison Gregory, Monika Hartig, Susan Hayflick, Andreas Hermann
    Abstract:

    NeuroAcanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasm

Ulrich Salzer - One of the best experts on this subject based on the ideXlab platform.

  • Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic
    PloS one, 2015
    Co-Authors: Jasmin Schiessl-weyer, Pedro Roa, Franco Laccone, Britta Kluge, Alexander Tichy, Euripedes De Almeida Ribeiro, Rainer Prohaska, Peter Stoeter, Claudia Siegl, Ulrich Salzer
    Abstract:

    Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the NeuroAcanthocytosis (NA) syndromes. It has not been investigated yet whether Acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed Acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, Acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated Acanthocytosis and the rest showing mild (6-10%) or no (

  • Acanthocytosis and the c 680 a g mutation in the pank2 gene a study enrolling a cohort of pkan patients from the dominican republic
    PLOS ONE, 2015
    Co-Authors: Jasmin Schiesslweyer, Pedro Roa, Franco Laccone, Britta Kluge, Alexander Tichy, Euripedes De Almeida Ribeiro, Rainer Prohaska, Peter Stoeter, Claudia Siegl, Ulrich Salzer
    Abstract:

    Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the NeuroAcanthocytosis (NA) syndromes. It has not been investigated yet whether Acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed Acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, Acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated Acanthocytosis and the rest showing mild (6-10%) or no (<6%) Acanthocytosis. Heterozygous control donors revealed a tendency to mild Acanthocytosis. Based on the insight that Pank2 is a normal constituent of red blood cells and de novo biosynthesis of coenzyme A is likely to take place in the erythrocyte cytosol we propose a hypothetical model that accounts for the variability in the occurrence of acanthocytic cells in PKAN.

Akira Sano - One of the best experts on this subject based on the ideXlab platform.

  • mouse model of chorea Acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece
    Biochemical and Biophysical Research Communications, 2018
    Co-Authors: Omi Nagata, Masayuki Nakamura, Hitoshi Sakimoto, Yuka Urata, Natsuki Sasaki, Nari Shiokawa, Akira Sano
    Abstract:

    Abstract Chorea-Acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and Acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60–61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5′-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.

  • seizures as presenting and prominent symptom in chorea Acanthocytosis with c 2343del vps13a gene mutation
    Epilepsia, 2016
    Co-Authors: Felix Benninger, Masayuki Nakamura, Akira Sano, Zaid Afawi, Amos D Korczyn, Karen L Oliver, Manuela Pendziwiat, Ingo Helbig, Samuel F Berkovic
    Abstract:

    Objective The aim of the study was to characterize the clinical features of nine patients in three families with chorea-Acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene. Methods Genetic test results, clinical description, magnetic resonance imaging (MRI), and electroencephalography (EEG), as well as laboratory results are summarized. Results ChAc is a rare genetic disorder characterized by hyperkinetic movements, seizures, cognitive decline, neuropsychiatric symptoms, and acanthocytes on peripheral blood smear. This unique cohort of nine patients is characterized by seizures as a first and prominent symptom. In our patients, other features of ChAc appeared later, including tics, other movement disorders, dysarthria, and mild to moderate cognitive decline. Significance Patients with chorea-Acanthocytosis carrying the described rare mutation can present with focal, treatment-resistant seizures.

  • Neurologic phenotypes associated with Acanthocytosis.
    Neurology, 2007
    Co-Authors: Ruth H. Walker, Akira Sano, Luca Rampoldi, Carol Dobson-stone, Hans H Jung, François Tison, Adrian Danek
    Abstract:

    The term "neuroAcanthocytosis" is normally used to refer to autosomal recessive chorea-Acanthocytosis and X-linked McLeod syndrome, but there are other movement disorders in which erythrocyte Acanthocytosis may also be seen, such as Huntington disease-like 2 and pantothenate kinase-associated neurodegeneration. Disorders of serum lipoproteins such as Bassen-Kornzweig disease form a distinct group of neuroAcanthocytosis syndromes in which ataxia is observed, but movement disorders are not seen. Genetic testing has enabled us to distinguish between these disorders, even when there are considerable similarities between phenotypes. Improved detection is important for accurate genetic counseling, for monitoring for complications, and, it is hoped, for implementing causal treatments, once these become available. As in other neurodegenerative conditions, animal models are a promising strategy for the development of such therapies.

  • Hereditary chorea--update
    Rinshō shinkeigaku Clinical neurology, 2004
    Co-Authors: Akira Sano
    Abstract:

    : Understanding molecular genetical background of hereditary chorea has recently been progressed so far. Triplet repeat expansion diseases including, Huntington disease, in which CAG expansion has been identified in the IT-15 or Huntingtin gene, and Huntington disease like-2, in which CTG expansion in junctophilin-3 (JPH3) gene occurs, causes selective degeneration of striatum in the brain. Octapeptide repeat expansion in the prion gene in Huntington disease like-1 has been also identified. NeuroAcanthocytosis syndromes including McLeod syndrome and chorea-Acanthocytosis cause Acanthocytosis in the red blood cells and chorea due to the degeneration of caudate nucleus in the brain. The XK gene on the X chromosome is mutated to lose its function in McLeod syndrome. CHAC gene coding chorein is mutated to lead loss of function in chorea-Acanthocytosis. Selective degeneration in the striatum, especially in the caudate nucleus might be associated with the molecular cascade of expanded polyglutamine or polyleucine or octapeptide and the loss of function of the XK protein and of chorein protein.

  • the gene encoding a newly discovered protein chorein is mutated in chorea Acanthocytosis
    Nature Genetics, 2001
    Co-Authors: Shuichi Ueno, Yoshiko Maruki, Masayuki Nakamura, Yuko Tomemori, Kazue Kamae, Hirotaka Tanabe, Yoriaki Yamashita, Seiji Matsuda, Sunao Kaneko, Akira Sano
    Abstract:

    Chorea-Acanthocytosis is a neurodegenerative disorder with peripheral red cell Acanthocytosis1. Linkage of chorea-Acanthocytosis to chromosome 9q21 has been found2. We refined the locus region and identified a previously unknown, full-length cDNA encoding a presumably structural protein, which we called chorein. We found a deletion in the coding region of the cDNA leading to a frame shift resulting in the production of a truncated protein in both alleles of patients and in single alleles of obligate carriers.

Ruth H. Walker - One of the best experts on this subject based on the ideXlab platform.

  • Absence of Acanthocytosis in Huntington’s Disease-like 2: A Prospective Comparison with Huntington’s Disease
    Tremor and other hyperkinetic movements (New York N.Y.), 2017
    Co-Authors: David G. Anderson, Dobrila D. Rudnicki, Russell L. Margolis, Ruth H. Walker, Sergio Carmona, Kubendran Naidoo, Theresa L. Coetzer, Jonathan Carr, Amanda Krause
    Abstract:

    Huntington's Disease-like 2 (HDL2) is classified as a neuroAcanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington's disease (HD). We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were prepared using international standards and reviewed by at least two blinded reviewers. An Acanthocytosis rate of greater than 1.2% in the dry smear or greater than 3.7% in the wet smear was designated a priori as the threshold for clinical significance based on previously established standards. Flow cytometry was performed on all but four of the cases. Red cell membrane protein analysis was performed on all participants. There were 12 HDL2, 13 HD, and 21 controls enrolled. None of the HD or HDL2 participants had defined Acanthocytosis or other morphological abnormalities. None of the HD or HDL2 cases had evidence of an abnormal band 3. Acanthocytosis was not identified in either HDL2 or HD in our patient population. Our results, based on the first prospective study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will not help establish the diagnosis of HD or HDL2, nor differentiate between the two disorders and raises the question if HDL2 should be placed within the neuroAcanthocytosis syndromes.

  • absence of Acanthocytosis in huntington s disease like 2 a prospective comparison with huntington s disease
    Tremor and other hyperkinetic movements (New York N.Y.), 2017
    Co-Authors: David G. Anderson, Dobrila D. Rudnicki, Russell L. Margolis, Ruth H. Walker, Sergio Carmona, Kubendran Naidoo, Theresa L. Coetzer, Jonathan Carr, Amanda Krause
    Abstract:

    Background:  Huntington’s Disease-like 2 (HDL2) is classified as a neuroAcanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington’s disease (HD). Methods:  We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were prepared using international standards and reviewed by at least two blinded reviewers. An Acanthocytosis rate of greater than 1.2% in the dry smear or greater than 3.7% in the wet smear was designated a priori as the threshold for clinical significance based on previously established standards. Flow cytometry was performed on all but four of the cases. Red cell membrane protein analysis was performed on all participants. Results:  There were 12 HDL2, 13 HD, and 21 controls enrolled. None of the HD or HDL2 participants had defined Acanthocytosis or other morphological abnormalities. None of the HD or HDL2 cases had evidence of an abnormal band 3. Discussion:  Acanthocytosis was not identified in either HDL2 or HD in our patient population. Our results, based on the first prospective study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will not help establish the diagnosis of HD or HDL2, nor differentiate between the two disorders and raises the question if HDL2 should be placed within the neuroAcanthocytosis syndromes.

  • hippocampal sclerosis and mesial temporal lobe epilepsy in chorea Acanthocytosis a case with clinical pathologic and genetic evaluation
    Neuropathology and Applied Neurobiology, 2017
    Co-Authors: Karin Mente, Adrian Danek, Christopher Grunseich, Marco M Hefti, John F Crary, Barbara I Karp, Ruth H. Walker
    Abstract:

    Chorea-Acanthocytosis (ChAc) is an autosomal recessive neurodegenerative disease associated with mutations in VPS13A that encodes the protein chorein. ChAc is characterized by progressive chorea, dystonia, and psychiatric symptoms, developing in young adulthood, often with Acanthocytosis in peripheral blood. Tongue protrusion, or feeding dystonia, is common, as are seizures and neuropathy [1]. On neuropathology, there is basal ganglia atrophy, neuronal loss, and gliosis, especially in the caudate nucleus [2]. We report the case of a patient with ChAc with hippocampal sclerosis who had extensive longitudinal follow-up, including neuropathology and general autopsy. This article is protected by copyright. All rights reserved.

  • Untangling the Thorns: Advances in the Neuroacantho- cytosis Syndromes
    2016
    Co-Authors: Ruth H. Walker
    Abstract:

    There have been significant advances in neuroac-anthocytosis (NA) syndromes in the past 20 years, however, confusion still exists regarding the pre-cise nature of these disorders and the correct no-menclature. This article seeks to clarify these is-sues and to summarise the recent literature in the field. The four key NA syndromes are described here–chorea-Acanthocytosis, McLeod syndrome, Huntington’s disease-like 2, and pantothenate ki-nase-associated neurodegeneration. In the first two, Acanthocytosis is a frequent, although not in-variable, finding; in the second two, it occurs in ap-proximately 10 % of patients. Degeneration affect-ing the basal ganglia is the key neuropathologi

  • NeuroAcanthocytosis Syndromes
    Orphanet Journal of Rare Diseases, 2011
    Co-Authors: Hans H Jung, Adrian Danek, Ruth H. Walker
    Abstract:

    NeuroAcanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell Acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-Acanthocytosis and X-linked McLeod syndrome which have a Huntington´s disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's disease-like 2, autosomal recessive pantothenate kinase-associated neurodegeneration and several inherited disorders of lipoprotein metabolism, namely abetalipoproteinemia (Bassen-Kornzweig syndrome) and hypobetalipoproteinemia leading to vitamin E malabsorption. The latter disorders are characterized by a peripheral neuropathy and sensory ataxia due to dorsal column degeneration, but movement disorders and cognitive impairment are not present. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway. Laboratory tests include blood smears to detect Acanthocytosis and determination of serum creatine kinase. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent in McLeod syndrome. Western blot for chorein demonstrates absence of this protein in red blood cells of chorea-Acanthocytosis patients. Specific genetic testing is possible in all NA syndromes. Differential diagnoses include Huntington disease and other causes of progressive hyperkinetic movement disorders. There are no curative therapies for NA syndromes. Regular cardiologic studies and avoidance of transfusion complications are mandatory in McLeod syndrome. The hyperkinetic movement disorder may be treated as in Huntington disease. Other symptoms including psychiatric manifestations should be managed in a symptom-oriented manner. NA syndromes have a relentlessly progressive course usually over two to three decades.

Andreas Hermann - One of the best experts on this subject based on the ideXlab platform.

  • Neurofilament light chain in serum is significantly increased in chorea-Acanthocytosis.
    Parkinsonism & Related Disorders, 2020
    Co-Authors: Kevin Peikert, Adrian Danek, Katja Akgün, Christian Beste, Tjalf Ziemssen, Carsten Buhmann, Andreas Hermann
    Abstract:

    Abstract Introduction Chorea-Acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease, characterized by hyper- and hypokinetic movement disorders, peripheral neuropathy and Acanthocytosis. Biomarkers are not established; possible candidates include neurofilament reflecting neuroaxonal damage. Methods We studied serum neurofilament light chain (sNfL) of six ChAc patients compared to two healthy control cohorts (A, six age/sex matched and B, historical cohort of 59 healthy adult subjects) and in two patients with the very similar condition of McLeod syndrome (MLS), the second core syndrome of neuroAcanthocytosis. sNfL was quantified using single-molecule array analysis. Results sNfL concentration was significantly higher in the ChAc cohort (18.73 pg/ml; IQR 15.65–27.70) compared to both healthy control cohorts (A, 7.37 pg/ml; IQR 5.60–9.05; B, 3.10 pg/ml; IQR 2.43–3.98). In MLS patients, a similar sNfL increase was observed. Conclusions sNfL is significantly increased in ChAc and MLS and seems to reflect neuroaxonal damage in the peripheral as well as the central nervous system.

  • Proceedings of the Ninth International Meeting on NeuroAcanthocytosis Syndromes
    Columbia University Libraries, 2018
    Co-Authors: Kevin Peikert, Andreas Hermann
    Abstract:

    The 9th International Meeting on NeuroAcanthocytosis Syndromes was held on March 23th–25th, 2018 in Dresden, Germany. The conference followed the tradition of the previous eight international symposia, the last of which was held in Ann Arbor, USA in May, 2016. Following the positive response to the previous meeting, a major component of this year’s symposium was the participation of patients, their families, and caregivers. The conference focused primarily on chorea-Acanthocytosis as one of the “core” diseases of neuroAcanthocytosis syndromes, with some discussion also of McLeod syndrome. These neurodegenerative diseases lead to chorea, epilepsy, cognitive and behavioral problems, and Acanthocytosis of red blood cells. While chorea-Acanthocytosis is caused by mutations in the VPS13A gene, other “VPS13opathies” (VPS13B-D) were also topic of the meeting. At present there are no treatments that can halt or slow down the progression of these diseases. However, two pathways seem to be prominently involved in chorea-Acanthocytosis – namely the PI3K (phosphoinositide 3-kinase) pathway and the Lyn kinase pathway – both of which are potential “druggable” targets. Model organisms including Dictyostelium, Drosophila, yeast, and mice, and human cell models were presented. Finally, clinical translation and clinical trial readiness in such a rare disease were extensively discussed

  • eighth international chorea Acanthocytosis symposium summary of workshop discussion and action points
    Tremor and other hyperkinetic movements (New York N.Y.), 2017
    Co-Authors: Samuel S Pappas, Adrian Danek, Lucia De Franceschi, Juan S Bonifacino, William T Dauer, Mithu De, Gilbert Dipaolo, Robert S Fuller, Volker Haucke, Andreas Hermann
    Abstract:

    Chorea-Acanthocytosis (ChAc) is a rare hereditary neurological disorder characterized by abnormal movements, red blood cell pathology, and progressive neurodegeneration. Little is understood of the pathogenesis of ChAc and related disorders (collectively NeuroAcanthocytosis). The Eighth International Chorea-Acanthocytosis Symposium was held in May 2016 in Ann Arbor, MI, USA, and focused on molecular mechanisms driving ChAc pathophysiology. Accompanying the meeting, members of the neuroAcanthocytosis research community and other invited scientists met in a workshop to discuss the current understanding and next steps needed to better understand ChAc pathogenesis. These discussions identified several broad and critical needs for advancing ChAc research and patient care, and led to the definition of 18 specific action points related to functional and molecular studies, animal models, and clinical research. These action points, described below, represent tractable research goals to pursue for the next several years.

  • Alterations of Red Cell Membrane Properties in
    2016
    Co-Authors: Claudia Siegl, Benedikt Bader, Adrian Danek, Patricia Hamminger, Herbert Jank, Uwe Ahting, Allison Gregory, Monika Hartig, Susan Hayflick, Andreas Hermann
    Abstract:

    NeuroAcanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasm

  • chorein sensitive polymerization of cortical actin and suicidal cell death in chorea Acanthocytosis
    The FASEB Journal, 2012
    Co-Authors: Michael Foller, Andreas Hermann, Shuchen Gu, Ioana Alesutan, Syed M Qadri, Oliver Borst, Evamaria Schmidt, Franziska Schiele, Jennifer Muller Vom Hagen, Carsten Saft
    Abstract:

    Chorea-Acanthocytosis is an inevitably lethal genetic disease characterized by a progressive hyperkinetic movement disorder and cognitive and behavioral abnormalities as well as Acanthocytosis. The...