Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilson's disease (WD) is a disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase, ATP7B. The WD incidence is approximately 1/50-10,000 live births worldwide. Clinical manifestations of WD may be of any kind, but usually the symptoms of presentation are hepatic or neuropsychiatric, with a vast range of disturbances for both groups of symptoms. In children, however, clinical symptoms may be absent, making the diagnosis of the disease more difficult than in adults. Hepatic manifestations may range from asymptomatic minor biochemical disturbances, to acute, but mostly chronic, hepatitis, cirrhosis or severe fulminant hepatic failure. The spectrum of neurological manifestations is wide, including tremor, hypersalivation, Dysarthria, coordination defects, dystonia, ataxia. The spectrum of psychiatric manifestations is considerable and may include different disturbances such as altered working performance, anxiety, depression and antisocial behaviour. Kayser-Fleischer rings (KF) are present in 95% of patients with neurological symptoms and somewhat over half of those without neurological symptoms. In children presenting with liver disease, KF rings are usually absent. To obtain a more reliable diagnosis of WD, the Leipzig scoring system was proposed by an international consensus of experts. Wilson's disease copper overload is treated with chelating agents such as penicillamine, trientine and tetrathiomolybdate. Zinc is used mostly for mantainance therapy or the treatment of asymptomatic WD patients.
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PMID:Wilson's disease. 2479 99

Neurological manifestations in liver diseases have been well-described. Parkinsonism developing in cirrhotic patients is a unique clinical, neuroradiological, and biological entity. The symptoms are often insidious in onset and occur after liver disease has made its presentation. Acute dysarthria as the presenting manifestation of cirrhosis is rare. Here we report three cases where liver disease made an unusual presentation as acute dysarthria. In all cases the abruptness of the onset prompted the treating physicians to make a diagnosis of stroke. The computed tomography (CT) scans of all these patients did not show any evidence of stroke. This was followed by magnetic resonance imaging (MRI) which showed the characteristic symmetric high-signal intensities in globus pallidus and substantia nigra in T1-weighted images, a reflection of increased tissue concentrations of manganese that helped in making a retrospective diagnosis of liver disease, confirmed later by altered serum albumin to globulin ratios and altered liver echo texture in ultra sonogram.
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PMID:Acute stroke-like presentation of acquired hepatocerebral degeneration. 2502 74

In paediatrics, one of our main aims in the diagnostic process is to identify any treatable conditions. The copper metabolism disorder Wilson's disease (WD) is one such condition that is caused by mutations in the ATP7B gene. Delay in treatment could result in irreversible disability or even death. Although liver disease is the most common presenting feature in children, some children may initially present with a subtle neurological presentation only. In patients presenting with dystonia, tremor, dysarthria or with a deterioration in school performance, there should be a high index of suspicion for WD. However, the differential of these clinical presentations is wide and exclusion of WD is difficult. No single diagnostic test can exclude WD and each of the biochemical tests has limitations. In this article, we discuss copper metabolism disorders including WD and Menke's disease. We then discuss the available diagnostic tests and how to investigate children for these rare disorders.
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PMID:How to use tests for disorders of copper metabolism. 2875 35

Wilson disease (WD) presents often as a chameleon with a plethora of mild and discrete symptoms. As disease of young aged people, the clinical diagnosis is extremely difficult and misdiagnoses are frequent. Tremor, dysarthria and hepatomegaly sometimes suggest alcoholic liver disease which is a disaster for the patients. Due to the only moderate abnormality of liver function tests the disease is underestimated in its severity with a fatal prognosis when not adequately treated. Therefore, it is the challenge to consider WD as diagnosis, particularly in young patients with unclear liver disease, neuropsychiatric disorders or hemolysis.
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PMID:Clinical features of Wilson disease. 3117 98

Neurologic symptoms in Wilson disease (WD) appear at an older age compared to hepatic symptoms and manifest in patients with misdiagnosed liver disease, in patients when the hepatic stage is clinically silent, in the case of non-compliance with anti-copper treatment, or with treatment failure. Neurologic symptoms in WD are caused by nervous tissue damage that is primarily a consequence of extrahepatic copper toxicity. Copper levels in brain tissues as well as cerebrospinal fluid (CSF) are diffusely increased by a factor of 10 and its toxicity involves various mechanisms such as mitochondrial toxicity, oxidative stress, cell membrane damage, crosslinking of DNA, and inhibition of enzymes. Excess copper is initially taken-up and buffered by astrocytes and oligodendrocytes but ultimately causes dysfunction of blood-brain-barrier and demyelination. Most severe neuropathologic abnormalities, including tissue rarefaction, reactive astrogliosis, myelin palor, and presence of iron-laden macrophages, are typically present in the putamen while other basal ganglia, thalami, and brainstem are usually less affected. The most common neurologic symptoms of WD are movement disorders including tremor, dystonia, parkinsonism, ataxia and chorea which are associated with dysphagia, dysarthria and drooling. Patients usually manifest with various combinations of these symptoms while purely monosymptomatic presentation is rare. Neurologic symptoms are largely reversible with anti-copper treatment, but a significant number of patients are left with residual impairment. The approach for symptomatic treatment in WD is based on guidelines for management of common movement disorders. The vast majority of WD patients with neurologic symptoms have abnormalities on brain magnetic resonance imaging (MRI). Pathologic MRI changes include T2 hyperintensities in the basal ganglia, thalami and white matter, T2 hypointensities in the basal ganglia, and atrophy. Most importantly, brain damage and neurologic symptoms can be prevented with an early initiation of anti-copper treatment. Introducing population WD screening, e.g., by exome sequencing genetic methods, would allow early treatment and decrease the neurologic burden of WD.
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PMID:Neurologic impairment in Wilson disease. 3117 1


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