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Adrian Danek - One of the best experts on this subject based on the ideXlab platform.
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Neurofilament light chain in serum is significantly increased in Chorea-Acanthocytosis.
Parkinsonism & Related Disorders, 2020Co-Authors: Kevin Peikert, Adrian Danek, Katja Akgün, Christian Beste, Tjalf Ziemssen, Carsten Buhmann, Andreas HermannAbstract: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.
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hippocampal sclerosis and mesial temporal lobe epilepsy in chorea acanthocytosis a case with clinical pathologic and genetic evaluation
Neuropathology and Applied Neurobiology, 2017Co-Authors: Karin Mente, Adrian Danek, Christopher Grunseich, Marco M Hefti, John F Crary, Barbara I Karp, Ruth H. WalkerAbstract: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.
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Early Diagnosis of Chorea-Acanthocytosis: Orofacial Dyskinesia, Epileptic Seizures, and HyperCKemia
Fortschritte der Neurologie-Psychiatrie, 2017Co-Authors: Christian Schneider, Adrian Danek, Arwed Hostmann, Gereon R Fink, Lothar BurghausAbstract: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).
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eighth international chorea acanthocytosis symposium summary of workshop discussion and action points
Tremor and other hyperkinetic movements (New York N.Y.), 2017Co-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 HermannAbstract: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.
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Chorea-Acanthocytosis presenting as dystonia.
Acta clinica Croatica, 2014Co-Authors: Jan Kobal, Adrian Danek, Carol Dobson-stone, Fidler, Bojana Zvan, Marjan ZaletelAbstract:Abstract The aim of this article is to present two Slovenian Chorea-Acanthocytosis (ChAc) siblings with an unusual predominantly dystonic ChAc phenotype. For diagnostic purposes, the genomic DNA was screened for VPS13A mutations. Movement disorder was evaluated and scored according to the Dystonia Movement and Disability Scale (DMDS) in order to evaluate the effects of L-dopa on dystonia. Brain imaging was performed with the use of magnetic resonance imaging scan and 99m Tc-ethyl cysteinate dimmer single photon emission computed tomography (Tc-ECD SPECT). Clinical neurological examination disclosed gait dystonia. Marked swallowing difficulty due to tongue and feeding dystonia was observed. Both siblings were found to be heterozygous for a substitution in exon 22 (c.2191C>T) and for a deletion in exon 35 (c.3995_3996delinsA) leading to mutation in VPS13A. After being administered L-dopa for three months, both subjects showed significant symptomatic improvement documented by reduced DMDS scores. It is concluded that VPS13A mutation testing may improve diagnosis of dystonia and recognition of atypical ChAc phenotypes. It seems that L-dopa could be effective in the treatment of dystonia due to VPS13A mutations.
Ruth H. Walker - One of the best experts on this subject based on the ideXlab platform.
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hippocampal sclerosis and mesial temporal lobe epilepsy in chorea acanthocytosis a case with clinical pathologic and genetic evaluation
Neuropathology and Applied Neurobiology, 2017Co-Authors: Karin Mente, Adrian Danek, Christopher Grunseich, Marco M Hefti, John F Crary, Barbara I Karp, Ruth H. WalkerAbstract: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.
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Axial Sensory Tricks in Chorea-Acanthocytosis: Insights into Phenomenology.
Tremor and other hyperkinetic movements (New York N.Y.), 2017Co-Authors: Roongroj Bhidayasiri, Onanong Jitkritsadakul, Ruth H. WalkerAbstract:Background: Trunk flexion and axial extension are characteristic symptoms of chorea–acanthocytosis (ChAc). Phenomenology Shown: A 41-year-old male with ChAc (confirmed by VPS13A mutations) reported that his involuntary axial movements were significantly ameliorated by either folding his arms over his chest or putting his hands behind his head. Educational Value: These apparent “sensory tricks” suggest a dystonic pathophysiology, and also merit further study to analyze their potential for symptom control in ChAc.
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Teaching Video NeuroImages: Feeding dystonia in Chorea-Acanthocytosis
Neurology, 2015Co-Authors: Martin Paucar, Ruth H. Walker, Per-Åke Lindestad, Per SvenningssonAbstract:A 39-year-old man was evaluated for personality change, involuntary movements, and eating difficulties. Examination demonstrated feeding dystonia, dysarthria, limb dystonia, and chorea (video on the Neurology ® Web site at [Neurology.org][1]). Transaminases and creatine kinase levels were elevated. Additional investigation revealed acanthocytes on blood smear, myopathy, and caudate nucleus atrophy (figures 1, 2, e-1, and e-2). Western blot revealed absent chorein, and a genetic test found him to be compound heterozygote for novel VPS13A gene mutations (c.266dupT and deletion of exons 52, 53, 55, and 58), establishing a diagnosis of Chorea-Acanthocytosis.1 He was treated with botulinum toxin injections in genioglossus, which significantly improved eating and speaking. Western blot analysis for chorein was performed by G. Kwiatkowski and Dr. Benedikt Bader with the financial support of the Advocacy for Neuroacanthocytosis Patients and of the ERA-net E-Rare consortium EMINA (European Multidisciplinary Initiative on Neuroacanthocytosis; BMBF 01GM1003) in the labs of Profs. Hans Kretzschmar/Armin Giese (Neuropathology) and Adrian Danek (Neurology) at Ludwig-Maximilians-Universitat, Munich, Germany. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000002108
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autosomal recessive transmission of chorea acanthocytosis confirmed
Acta Neuropathologica, 2012Co-Authors: Adrian Danek, Benedikt Bader, Antonio Velayosbaeza, Ruth H. WalkerAbstract:We would like to draw attention to new genetic data recently reported [8] on a patient previously described as suffering from Chorea-Acanthocytosis (ChAc) with autosomal dominant transmission [7] and for whom neuropathological findings were published in this journal in 2009 [4]. At that time we questioned the apparent inheritance, given the limitations of the molecular methodology employed, and the lack of support for this mode of transmission otherwise found [2]. A correction concerning the original publication by Saiki et al. [7] has recently been published [1] stating: “an error in sequencing occurred and the inheritance pattern should have been reported as autosomal recessive (pseudodominant)”. This erratum reflects the findings reported by Tomiyasu et al. [8] whose patient no. 22 was identified with III-3 from the pedigree originally published and is identical with the patient in whom autopsy findings had been described in this journal [4]. This subject was also reported as case 1 of a further clinical study [6]. The new molecular findings describe compound heterozygous VPS13A mutations in him and also in his affected sister: 1305G>A in exon 15 and 8035G>A in exon 57. The nomenclature of the latter mutation was corrected from 8295G>A in the original report [4, 7]. The patients’ mother (II-4) was shown to be an asymptomatic carrier of a single heterozygous 1305G>A mutation. The father of the postmortem case of Ishida et al. [4], by conclusion a carrier of the 8035G>A mutation, was said to be suffering from early onset hyperkinesia as did other family members [5]. Unfortunately, no further analyses on DNA were feasible and the presence of mutations in other genes, e.g., IT15, responsible for the supposedly dominant features observed in this man, his father, his two sisters and a sister’s son could not be investigated [7]. In addition, there is still a possibility of subclinical involvement in subjects who carry a single heterozygous VPS13A mutation although, so far, no convincing evidence has yet been put forward to support that claim [3, 9]. In summary, the suggestion of dominant transmission of a condition recognized as an autosomal recessive trait (OMIM 200150) has eventually been put to rest in the autopsy case reported in this journal in 2009 and one source of confusion has been removed.
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Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing
Movement Disorders, 2011Co-Authors: Ruth H. Walker, Vincent P. Schulz, Irina Tikhonova, Milind Mahajan, Shrikant Mane, Maritza Arroyo Muniz, Patrick G. GallagherAbstract:Neuroacanthocytoses are neurodegenerative disorders marked by phenotypic and genetic heterogeneity. There are several associated genetic loci, and many defects, including gene deletions and insertions, and missense, nonsense, and splicing mutations, have been found spread over hundreds of kilobases of genomic DNA. In some cases, specific diagnosis is unclear, particularly in the early stages of disease or when there is an atypical presentation. Determination of the precise genetic defect allows assignment of the diagnosis and permits carrier detection and genetic counseling. The objective of this report was to utilize exome sequencing for genetic diagnosis in the neuroacanthocytosis syndromes. Genomic DNA from 2 patients with clinical features of Chorea-Acanthocytosis was subjected to targeted exon capture. Captured DNA was subjected to ultrahigh throughput next-generation sequencing. Sequencing data were assembled, filtered against known human variant genetic databases, and results were analyzed. Both patients were compound heterozygotes for mutations in the VPS13A gene, the gene associated with Chorea-Acanthocytosis. Patient 1 had a 4-bp deletion that removes the 5′ donor splice site of exon 58 and a nucleotide substitution that disrupts the 5′ donor splice site of exon 70. Patient 2 had a dinucleotide deletion in exon 16 and a dinucleotide insertion in exon 33. No mutations were identified in the XK, PANK2, or JPH3 gene loci. Exome sequencing is a valuable diagnostic tool in the neuroacanthocytosis syndromes. These studies may provide a better understanding of the function of the associated proteins and provide insight into the pathogenesis of these disorders. © 2011 Movement Disorder Society
Susanne A. Schneider - One of the best experts on this subject based on the ideXlab platform.
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huntington s disease huntington s disease look alikes and benign hereditary chorea what s new
Movement Disorders Clinical Practice, 2016Co-Authors: Susanne A. Schneider, Thomas D BirdAbstract:Background: The differential diagnosis of chorea syndromes is complex. It includes inherited forms, the most common of which is autosomal dominant Huntington's disease (HD). In addition, there are disorders mimicking HD, the so-called HD-like (HDL) syndromes. Methods and Results: Here we review main clinical, genetic, and pathophysiological characteristics of HD and the rare HD phenocopies in order to familiarize clinicians with them. Molecular studies have shown that HD phenocopies account for about 1% of suspected HD cases, most commonly due to mutations in C9orf72 (also the main cause of frontotemporal dementia and amyotrophic lateral sclerosis syndromes), TATA box-binding protein (spinocerebellar ataxia type 17 [SCA17]/HDL4), and JPH3 (HDL2). Systematic screening studies also revealed mutations in PRNP (prion disease), VPS13A (Chorea-Acanthocytosis), ATXN8OS-ATXN8 (SCA8), and FXN (late-onset Friedreich's Ataxia) in single cases. Further differential diagnoses to consider in patients presenting with a clinical diagnosis consistent with HD, but without the HD expansion, include dentatorubral-pallidoluysian atrophy and benign hereditary chorea (TITF1), as well as the recently described form of ADCY5-associated neurodegeneration. Lastly, biallelic mutations in RNF216 and FRRS1L have recently been reported as autosomal recessive phenocopies of HD. Conclusion: There is a growing list of genes associated with chorea, yet a substantial percentage of patients remain undiagnosed. It is likely that more genes will be discovered in the future and that the clinical spectrum of the described disorders will broaden.
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characteristic head drops and axial extension in advanced chorea acanthocytosis
Movement Disorders, 2010Co-Authors: Benedikt Bader, Adrian Danek, Susanne A. Schneider, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis. (C) 2010 Movement Disorder Society
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Characteristic head drops and axial extension in advanced Chorea-Acanthocytosis.
Movement Disorders, 2010Co-Authors: Susanne A. Schneider, Benedikt Bader, Adrian Danek, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis.
Benedikt Bader - One of the best experts on this subject based on the ideXlab platform.
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autosomal recessive transmission of chorea acanthocytosis confirmed
Acta Neuropathologica, 2012Co-Authors: Adrian Danek, Benedikt Bader, Antonio Velayosbaeza, Ruth H. WalkerAbstract:We would like to draw attention to new genetic data recently reported [8] on a patient previously described as suffering from Chorea-Acanthocytosis (ChAc) with autosomal dominant transmission [7] and for whom neuropathological findings were published in this journal in 2009 [4]. At that time we questioned the apparent inheritance, given the limitations of the molecular methodology employed, and the lack of support for this mode of transmission otherwise found [2]. A correction concerning the original publication by Saiki et al. [7] has recently been published [1] stating: “an error in sequencing occurred and the inheritance pattern should have been reported as autosomal recessive (pseudodominant)”. This erratum reflects the findings reported by Tomiyasu et al. [8] whose patient no. 22 was identified with III-3 from the pedigree originally published and is identical with the patient in whom autopsy findings had been described in this journal [4]. This subject was also reported as case 1 of a further clinical study [6]. The new molecular findings describe compound heterozygous VPS13A mutations in him and also in his affected sister: 1305G>A in exon 15 and 8035G>A in exon 57. The nomenclature of the latter mutation was corrected from 8295G>A in the original report [4, 7]. The patients’ mother (II-4) was shown to be an asymptomatic carrier of a single heterozygous 1305G>A mutation. The father of the postmortem case of Ishida et al. [4], by conclusion a carrier of the 8035G>A mutation, was said to be suffering from early onset hyperkinesia as did other family members [5]. Unfortunately, no further analyses on DNA were feasible and the presence of mutations in other genes, e.g., IT15, responsible for the supposedly dominant features observed in this man, his father, his two sisters and a sister’s son could not be investigated [7]. In addition, there is still a possibility of subclinical involvement in subjects who carry a single heterozygous VPS13A mutation although, so far, no convincing evidence has yet been put forward to support that claim [3, 9]. In summary, the suggestion of dominant transmission of a condition recognized as an autosomal recessive trait (OMIM 200150) has eventually been put to rest in the autopsy case reported in this journal in 2009 and one source of confusion has been removed.
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Chorea-Acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred.
Archives of Neurology, 2011Co-Authors: Antonio Velayos-baeza, Benedikt Bader, Adrian Danek, Anthony P. Monaco, Elke Holinski-feder, Birgit Neitzel, Edmund M. R. Critchley, Ruth H. WalkerAbstract:Objective To determine the molecular nature of the neurological disease in the seminal family reported by Critchley et al in the 1960s, characterized by a hyperkinetic movement disorder and the appearance of acanthocytosis on peripheral blood smear. The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion. Design DNA analysis. Setting Molecular biology research laboratories. Participants First- and second-degree relatives of the original Critchley et al proband from Kentucky. Main Outcome Measures Mutations in the VPS13A gene. Results A mutation was identified in the VPS13A gene, responsible for autosomal recessive Chorea-Acanthocytosis. Haplotype reconstruction suggested that this mutation was homozygous in the proband. Conclusion These findings strongly support the diagnosis of Chorea-Acanthocytosis as the disorder described in the original report.
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Bilateral temporal lobe epilepsy confirmed with intracranial EEG in Chorea-Acanthocytosis
Seizure, 2011Co-Authors: Benedikt Bader, Christian Vollmar, Nibal Ackl, Anne Ebert, Christian La Fougère, Soheyl Noachtar, Adrian DanekAbstract:Chorea-Acanthocytosis (ChAc) is an uncommon basal ganglia disorder, in which the movement disorder element may be obscured by the predominance of seizures. We report a pertinent case of a patient who had undergone extensive evaluation for epilepsy, including intracranial EEG before finally the diagnosis of ChAc was made and confirmed by Western blot. We suggest that in patients with epilepsy, particularly of temporal lobe origin and with onset in the third decade with inconclusive findings on clinical examination and neuroimaging such as dyskinesias, dystonia and basal ganglia involvement, ChAc should be considered.
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characteristic head drops and axial extension in advanced chorea acanthocytosis
Movement Disorders, 2010Co-Authors: Benedikt Bader, Adrian Danek, Susanne A. Schneider, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis. (C) 2010 Movement Disorder Society
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Characteristic head drops and axial extension in advanced Chorea-Acanthocytosis.
Movement Disorders, 2010Co-Authors: Susanne A. Schneider, Benedikt Bader, Adrian Danek, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis.
Kailash P Bhatia - One of the best experts on this subject based on the ideXlab platform.
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characteristic head drops and axial extension in advanced chorea acanthocytosis
Movement Disorders, 2010Co-Authors: Benedikt Bader, Adrian Danek, Susanne A. Schneider, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis. (C) 2010 Movement Disorder Society
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Characteristic head drops and axial extension in advanced Chorea-Acanthocytosis.
Movement Disorders, 2010Co-Authors: Susanne A. Schneider, Benedikt Bader, Adrian Danek, Elena Moro, Anthony E Lang, Kailash P BhatiaAbstract:Chorea-Acanthocytosis is a rare autosomal recessive neurodegenerative disorder with a complex clinical presentation comprising of a mixed movement disorder (mostly chorea and dystonia), seizures, neuropathy and myopathy, autonomic features as well as dementia and psychiatric features. Because the differential diagnosis is wide, clinical clues and red flags are important. We report here our observation of characteristic neck and trunk flexion and extension spasms in four cases with advanced Chorea-Acanthocytosis.