Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis (MS) is a demyelinating disease characterized by an unpredictable clinical course with intermittent relapses that lead over time to significant neurological disability. Clinical and radiological variables are limited in the ability to predict disease course. Peripheral blood genome scale analyses were used to characterize MS patients with different disease types, but not for prediction of outcome. Using complementary-DNA microarrays we studied peripheral-blood gene expression patterns in 53 relapsing-remitting MS patients. Patients were classified into good, intermediate and poor clinical outcome established after 2-year follow-up. A training set of 26 samples was used to identify clinical outcome differentiating gene-expression signature. Supervised learning and feature selection algorithms were applied to identify a predictive signature that was validated in an independent group of 27 patients. Key genes within the predictive signature were confirmed by quantitative reverse transcription-polymerase chain reaction in an additional 10 patients. The analysis identified 431 differentiating genes between patients with good and poor clinical outcome (change in neurological disability by the expanded disability status scale was -0.33 +/- 0.24 and 1.6 +/- 0.35, P = 0.0002, total number of relapses were 0 and 1.80 +/- 0.35, P = 0.00009, respectively). An optimal set of 29 genes was depicted as a clinical outcome predictive gene expression signature and classified appropriately 88.9% of patients. This predictive signature was enriched by genes related biologically to zinc-ion binding and cytokine activity regulation pathways involved in inflammation and apoptosis. Our findings provide a basis for monitoring patients by prediction of disease outcome and can be incorporated into clinical decision-making in relapsing-remitting MS.
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PMID:Zinc-ion binding and cytokine activity regulation pathways predicts outcome in relapsing-remitting multiple sclerosis. 1748 94

Wilson disease is an autosomal recessive disease that produces a copper accumulation in many organs, initially in the liver, progressing to liver cirrhosis, and in the brain, with different neurologic symptoms. Diagnosis is based on clinical, biochemical, and genetic tests. Different treatments based on chelating agents may help reduce the disease's spontaneous morbidity and mortality. We describe three patients who presented Wilson disease before 18 years of age, with initial neurologic symptoms between 1998 and 2010. After comparison with literature reports, their clinical symptoms, progression, and care allowed us to propose a treatment algorithm. Neurologic symptoms are present in 35% of the patients with Wilson disease such as dystonia, extrapyramidal syndrome, dysarthria, dysphagia, and psychiatric symptoms. The time to diagnosis remains too long and may account for the increased severity of the illness encountered and problems treating these patients. The first treatment choice must be triethylenetetramine, which causes fewer side effects of initial worsening of symptoms compared to D-penicillamine. Zinc therapy is the first treatment for asymptomatic patients or those on maintenance treatment. Finally, liver transplantation is a potential treatment even if the patient presents severe neurological disability because it may improve clinical symptoms. However, further research is warranted on this matter.
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PMID:[Diagnosis and care of Wilson disease with neurological revelation]. 2226 Dec 59

Wilson disease is a rare, inherited autosomal recessive disease of copper metabolism and may be more common where consanguinity is prevalent. Much has been known about the disease after it was first described by Kinnier Wilson as 'progressive lenticular degeneration in 1912. Over 500 mutations of the ATP7B gene has been identified with no clear genotype to phenotype correlation. Loss of ATP7B function leads various grades of reduced biliary excretion of copper and reduced incorporation of copper into ceruloplasmin; accumulation and toxicity of copper in the liver, brain and other tissues results in liver toxicity and other myriad manifestations of the disease. The clinical features may vary from asymptomatic state to chronic liver disease, acute liver failure, neuropsychiatric manifestations and hemolytic anemia. Diagnosis is based on the combination of clinical sign's, biochemical features, histologic findings and mutation analysis of ATP7B gene. Subtle geographical differences exist with a disproportionate proportion of children presenting with acute liver failure. A high index of suspicion is needed for an early diagnosis. Ratios of biochemical indices for early diagnosis need validation across geographical regions and may not be particularly applicable in children. Better biomarkers or the need for tests for early detection of ALF persists. Drugs used in the treatment of Wilson disease include copper chelating agents such as d-Penicillamine, trientine and zinc salt. Untreated Wilson disease uniformly leads to death from liver disease or severe neurological disability. Early recognition and treatment has excellent prognosis. Liver transplantation is indicated in acute liver failure and end stage liver disease. Family screening in order to detect the disorder in the first-degree relatives is warranted. This review provides an overview of different aspects of Wilson disease including geographical differences in presentations and clinical management and the limitations of currently available tests.
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PMID:A review and current perspective on Wilson disease. 2575 20