Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated "acanthocytic" red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington's disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.
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PMID:Clinical and molecular research of neuroacanthocytosis. 2520 31

There have been significant advances in neuroacanthocytosis (NA) syndromes in the past 20 years, however, confusion still exists regarding the precise nature of these disorders and the correct nomenclature. This article seeks to clarify these issues 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 kinase- associated neurodegeneration. In the first two, acanthocytosis is a frequent, although not invariable, finding; in the second two, it occurs in approximately 10% of patients. Degeneration affecting the basal ganglia is the key neuropathologic finding, thus the clinical presentations can be remarkably similar. The characteristic phenotype comprises a variety of movement disorders, including chorea, dystonia, and parkinsonism, and also psychiatric and cognitive symptoms attributable to basal ganglia dysfunction. The age of onset, inheritance patterns, and ethnic background differ in each condition, providing diagnostic clues. Other investigations, including routine blood testing and neuroimaging can be informative. Genetic diagnosis, if available, provides a definitive diagnosis, and is important for genetic counseling, and hopefully molecular therapies in the future. In this article I provide a historical perspective on each NA syndrome. The first 3 disorders, chorea-acanthocytosis, McLeod syndrome, Huntington's disease-like 2, are discussed in detail, with a comprehensive review of the literature to date for each, while pantothenate kinase-associated neurodegeneration is presented in summary, as this disorder has recently been reviewed in this journal. Therapy for all of these diseases is, at present, purely symptomatic.
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PMID:Untangling the Thorns: Advances in the Neuroacanthocytosis Syndromes. 2609 76

Chorea-acanthocytosis (ChAc), a neurodegenerative disease, results from loss-of-function-mutations of the chorein-encoding gene VPS13A. Affected patients suffer from a progressive movement disorder including chorea, parkinsonism, dystonia, tongue protrusion, dysarthria, dysphagia, tongue and lip biting, gait impairment, progressive distal muscle wasting, weakness, epileptic seizures, cognitive impairment, and behavioral changes. Those pathologies may be paralleled by erythrocyte acanthocytosis. Chorein supports activation of phosphoinositide-3-kinase (PI3K)-p85-subunit with subsequent up-regulation of ras-related C3 botulinum toxin substrate 1 (Rac1) activity, p21 protein-activated kinase 1 (PAK1) phosphorylation, and activation of several tyrosine kinases. Chorein sensitive PI3K signaling further leads to stimulation of the serum and glucocorticoid inducible kinase SGK1, which in turn upregulates ORAI1, a Ca2+-channel accomplishing store operated Ca2+-entry (SOCE). The signaling participates in the regulation of cytoskeletal architecture on the one side and cell survival on the other. Compromised cytoskeletal architecture has been shown in chorein deficient erythrocytes, fibroblasts and endothelial cells. Impaired degranulation was observed in chorein deficient PC12 cells and in platelets from ChAc patients. Similarly, decreased ORAI1 expression and SOCE as well as compromised cell survival were seen in fibroblasts and neurons isolated from ChAc patients. ORAI1 expression, SOCE and cell survival can be restored by lithium treatment, an effect disrupted by pharmacological inhibition of SGK1 or ORAI1. Chorein, SGK1, ORAI1 and SOCE further confer survival of tumor cells. In conclusion, much has been learned about the function of chorein and the molecular pathophysiology of chorea-acanthocytosis. Most importantly, a treatment halting or delaying the clinical course of this devastating disease may become available. A controlled clinical study is warranted, in order to explore whether the in vitro observations indeed reflect the in vivo pathology of the disease.
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PMID:Neurons, Erythrocytes and Beyond -The Diverse Functions of Chorein. 2917 76

Heralded by obsessive-compulsive disorder and anxiety, chorea-acanthocytosis may initially present in a psychiatric setting. As insidious onset of involuntary movements is commonly precipitated by dopamine blocking agents, this may not prompt further neurological investigation until symptoms progress after withdrawal of the suspected offending drug. Oromandibular dystonia and frontal disinhibition should call for early neurologic evaluation.
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PMID:Criminal Behaviour Associated with a Novel Mutation in the VPS13A-Gene Causing Chorea-Acanthocytosis. 3113 85

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatment in Parkinson's disease (PD) but much less frequently targeted for other disorders. Here we report the results of simultaneous local field potential (LFP) recordings and magnetoencephalography (MEG) in a single patient who was implanted bilaterally in the STN for the treatment of dystonia induced by chorea-acanthocytosis. Consistent with the previous results in PD, the dystonia patient showed significant subthalamo-cortical coherence in the high beta band (28-35 Hz) on both sides localized to the mesial sensorimotor areas. In addition, on the right side, significant coherence was found in the theta-alpha band (4-12 Hz) that localized to the medial prefrontal cortex with the peak in the anterior cingulate gyrus. Comparison of STN power spectra with a previously reported PD cohort showed increased power in the theta and alpha bands and decreased power in the low beta band in dystonia which is consistent with most of the previous studies. The present report extends the range of disorders for which cortico-subthalamic oscillatory connectivity has been characterized. Our results strengthen the evidence that at least some of the subthalamo-cortical oscillatory coherent networks are a feature of the healthy brain, although we do not rule out that coherence magnitude could be affected by disease.
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PMID:Cortico-subthalamic Coherence in a Patient With Dystonia Induced by Chorea-Acanthocytosis: A Case Report. 3119 Dec 73

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek, and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after DBS surgery. Here, we present a case of ChAc in a 31-year-old male positive for VPS13A gene mutations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. DBS using monopolar stimulation with placement slightly lateral to the GPi was associated with significant improvement in chorea and dysarthria. This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact and ideal target of DBS in ChAc.
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PMID:Efficacy of Deep Brain Stimulation in a Patient with Genetically Confirmed Chorea-Acanthocytosis. 3154 3


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