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)

Tardive dystonia is an uncommon but intractable and distressing complication of neuroleptic treatment. It is suggested that individual predisposing vulnerability plays a major role in the development of the side effect. This study aimed to investigate relationship tardive dystonia and several genetic factors such as polymorphism of cytochrome P4502D6, and receptor polymorphisms of dopamine D(2) (TaqI A and -141C Ins/Del polymorphisms) and D(3) (Ser(9)Gly polymorphism). Nine patients with tardive dystonia were genotyped for these genetic polymorphisms. No specific genotypes or alleles were overpresented in the patients. This study suggests that these polymorphisms are not related to the development of tardive dystonia.
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PMID:Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2 and D3 receptors: a preliminary finding. 1221 Feb 90

The combination of optic atrophy and dystonia has been etiologically associated with mitochondrial DNA (mtDNA) mutations. We report here on the complete mtDNA sequence from the proband of a consanguineous family exhibiting "mitochondrial-like" optic atrophy and dystonia. A candidate tRNA(Gly) mutation was identified that was unique to the family. However, the mutation was homoplasmic in both affected and unaffected family members and we were unable to demonstrate a biochemical defect in patient mitochondria. Hence, it is unlikely that a mtDNA mutation accounts for the phenotype in this family.
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PMID:Complete mitochondrial DNA sequence analysis in a family with early-onset dystonia and optic atrophy. 1497 86

The neurotransmitter disorders represent an enigmatic and enlarging group of neurometabolic conditions caused by abnormal neurotransmitter metabolism or transport. A high index of clinical suspicion is important, given the availability of therapeutic strategies. This article covers disorders of monoamine (catecholamine and serotonin) synthesis, glycine catabolism, pyridoxine dependency, and gamma-aminobutyric acid (GABA) metabolism. The technological aspects of appropriate cerebrospinal fluid (CSF) collection, shipment, study, and interpretation merit special consideration. Diagnosis of disorders of monoamines requires analysis of CSF homovanillic acid, 5-hydroxyindoleacetic acid, ortho-methyldopa, BH4, and neopterin. The delineation of new disorders with important therapeutic implications, such as cerebral folate deficiency and PNPO deficiency, serves to highlight the value of measuring CSF neurotransmitter precursors and metabolites. The impressive responsiveness of Segawa fluctuating dystonia to levodopa is a hallmark feature of previously unrecognized neurologic morbidity becoming treatable at any age. Aromatic amino acid decarboxylase and tyrosine hydroxylase deficiency have more severe phenotypes and show variable responsiveness to levodopa. Glycine encephalopathy usually has a poor outcome; benzoate therapy may be helpful in less affected cases. Pyridoxine-dependent seizures are a refractory but treatable group of neonatal and infantile seizures; rare cases require pyridoxal-5-phosphate. Succinic semialdehyde dehydrogenase deficiency is relatively common in comparison to the remainder of this group of disorders. Treatment directed at the metabolic defect with vigabatrin has been disappointing, and multiple therapies are targeted toward specific but protean symptoms. Other disorders of GABA metabolism, as is true of the wide spectrum of neurotransmitter disorders, will require increasing use of CSF analysis for diagnosis, and ultimately, treatment.
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PMID:Diagnosis and treatment of neurotransmitter disorders. 1703 64

Dystonia-1 (DYT1) is an autosomal dominant early-onset torsion form of dystonia, a neurological disease affecting movement. DYT1 is the prototypic hereditary dystonia and is caused by the mutation of the tor1a gene. The gene product has chaperone functions important for the control of protein folding and stability. Dystonia-4 (DYT4) is another autosomal dominant dystonia that is characterized by onset in the second to third decade of progressive laryngeal dysphonia. DYT4 is associated with the mutation of the tubb4a gene, although it remains to be understood how disease-associated mutation affects biochemical as well as cell biological properties of the gene product as the microtubule component (a tubulin beta subunit). Herein we demonstrate that DYT4-associated TUBB4A missense mutants (Arg2-to-Gly or Ala271-to-Thr) form disorganized tubulin networks in cells. Transfected mutants are indeed expressed in cytoplasmic regions, as observed in wild-type transfectants. However, mutant proteins do not exhibit typical radial tubulin networks. Rather, they have diminished ability to interact with tubulin alpha subunits. Processes do not form in sufficient amounts in cells of the N1E-115 neuronal cell line expressing each of these mutants as compared to parental cells. Together, DYT4-associated TUBB4A mutants themselves form aberrant tubulin networks and inhibit neuronal process growth, possibly explaining progress through the pathological states at cellular levels.
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PMID:Dystonia-4 (DYT4)-associated TUBB4A mutants exhibit disorganized microtubule networks and inhibit neuronal process growth. 2912 12