Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical spectrum of spinocerebellar ataxia 3 (SCA 3) disease is wide and varied. We describe a Chinese patient with a mutation at the SCA 3 locus with clinical features of levodopa-responsive dystonia. The family history was suggestive of being autosomally dominant. Levodopa responsiveness though rare has been described in families with features of parkinsonism. Noteworthy is the relatively late onset of disease (>40 years) possibly explained by the low number of affected alleles at 59, the usual range being from 62 to 86, with the lowest recorded number at 56. This expands the wide and varied phenotypic manifestations of SCA 3, and highlights the observation that features suggestive of levodopa-responsive dystonia (DRD) such as focal dystonia, gait difficulty with diurnal fluctuation of symptoms, and a marked response to low doses of levodopa can be presenting features of SCA 3. SCA 3 should be considered a differential diagnosis in adult patients who present with DRD phenotype and with a positive family history.
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PMID:Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family. 1287 51

Clinical heterogeneity is the prominent feature of spinocerebellar ataxia type 3 (SCA3) which is sometimes neglected and often impedes the timely diagnosis of patients. In this study, the clinical data of 201 unrelated Chinese SCA3 patients were retrospectively studied. The rare clinical features were summarized and the underlying genetic mutations were screened by direct DNA sequencing. Three patients were found primarily presenting with the rare clinical features, including dystonic phenotype without response to levodopa, chorea and memory decline, and hearing impairment, respectively. We firstly reported three diverse heterogeneities of SCA3 patients, which are quite uncommon in the Chinese SCA3 patients. Our results expanded the variable phenotypes of SCA3 and provided the explicit information for the rare and special SCA3 manifestations. Based on this new knowledge, we suggested that when the presentation was consistent with HD or DRD while negative in the corresponding genetic testing, SCA3 should be considered, and clinicians should divert partial attention to the examinations on the auditory system of SCA3 patients.
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PMID:Chinese patients with spinocerebellar ataxia type 3 presenting with rare clinical symptoms. 2341 47

Progressive dystonias are a clinically and genetically heterogeneous group of movement disorders. In the primary forms, dystonia is the only sign of the disease, and the cause is either unknown or genetic. In the secondary forms, dystonia is usually only one of several disease manifestations and the cause may be genetic or due to other insults. Monogenic defects have been found to underlie many forms of dystonia syndromes, which are designated DYT1-20. Dystonias with known genes include DYT1 and DYT6 dystonia, presenting as isolated torsion dystonia, as well as DYT5 (dopa-responsive dystonia), DYT11 (myoclonus-dystonia), and DYT12 (rapid-onset dystonia-parkinsonism), where dystonia occurs in conjunction with other types of movement disorders. All of these conditions follow an autosomal dominant mode of inheritance, usually develop in childhood or early adolescence, and show an initially progressive course with stabilization in early adulthood. In secondary dystonias, there are often atypical features and additional neurological signs, such as prominent tongue and perioral involvement, pyramidal signs, ataxia, oculomotor abnormalities, or cognitive disturbances. Acquired brain lesions typically affect the putamen, thalamus, or globus pallidus and cause contralateral hemidystonia. Dystonia can be part of the clinical syndrome in many heredodegenerative disorders, or may be drug-induced or psychogenic.
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PMID:Progressive dystonia. 2362 12

Previously, we defined DRD as a syndrome of selective nigrostriatal dopamine deficiency caused by genetic defects in the dopamine synthetic pathway without nigral cell loss. DRD-plus also has the same etiologic background with DRD, but DRD-plus patients have more severe features that are not seen in DRD because of the severity of the genetic defect. However, there have been many reports of dystonia responsive to dopaminergic drugs that do not fit into DRD or DRD-plus (genetic defects in the dopamine synthetic pathway without nigral cell loss). We reframed the concept of DRD/DRD-plus and proposed the concept of DRD look-alike to include the additional cases described above. Examples of dystonia that is responsive to dopaminergic drugs include the following: transportopathies (dopamine transporter deficiency; vesicular monoamine transporter 2 deficiency); SOX6 mutation resulting in a developmentally decreased number of nigral cells; degenerative disorders with progressive loss of nigral cells (juvenile Parkinson's disease; pallidopyramidal syndrome; spinocerebellar ataxia type 3), and disorders that are not known to affect the nigrostriatal dopaminergic system (DYT1; GLUT1 deficiency; myoclonus-dystonia; ataxia telangiectasia). This classification will help with an etiologic diagnosis as well as planning the work up and guiding the therapy.
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PMID:Expanding the Spectrum of Dopa-Responsive Dystonia (DRD) and Proposal for New Definition: DRD, DRD-plus, and DRD Look-alike. 2998 92

Parkinson's disease (PD) is a common neurodegenerative disorder. In 2015, The Movement Disorder Society Clinical Diagnostic Criteria for PD was published. In the criteria, the absolute exclusion criteria and red flags were designed to minimize diagnostic error, in particular to differentiate from neurodegenerative or secondary parkinsonism. Here, we reviewed neurodegenerative disorders that we should differentiate from PD. The common differential diagnoses, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, and essential tremor are important but sometimes difficult to differentiate. We also described the features of rare but important differential diagnoses: neuronal intranuclear inclusion disease, Perry syndrome, Fragile X tremor/ataxia syndrome, Huntington's disease, dopa-responsive dystonia, Wilson disease, and neurodegeneration wit,1 brain iron accumulation.
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PMID:Differential diagnosis of Parkinson's disease and other neurodegenerative disorders. 3056 95