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)

In a 21-year-old woman with a smaller and sloppy handwriting, drooling especially when stooping, sporadic choking, clumsiness, and frequent stumbling, Wilson's disease was diagnosed. The medical history disclosed a short period of haemolytic anaemia with transient hepatic failure, and irregular menstruation periods with infertility. On examination there were no signs of liver or spleen enlargement. She was slow, had an expressionless face and mild dysarthria, and slight impairment of the coordination of the limbs. Magnetic resonance imaging of the brain showed bilateral hyperintensive lesions of the basal ganglia on T2W images. Zinc therapy induced a good biochemical response and there was also some clinical improvement. Linkage analysis within the family identified one other asymptomatic homozygotically affected sister. A diagnostic delay occurs frequently due to relative unfamiliarity with this rare disease and due to its variable clinical expression.
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PMID:[Wilson's disease; diagnosis with the aid of magnetic resonance tomography]. 772 83

Kennedy's disease (spinal and bulbar muscular atrophy) is an X-linked form of motor neuron disease that affects adult men. The syndrome is characterized by progressive atrophy of the limb muscles, pelvic and shoulder girdles and dysphagia and dysarthria, and is caused by the degeneration of spinal and bulbar motor neurons. Kennedy's disease is caused by a trinucleotide repeat expansion of a CAG repeat in exon A of the androgen receptor gene, and is one of a group of neurological diseases caused by trinucleotide repeat expansions in different genes. The mutation in Kennedy's disease involves an increased number of glutamine residues in the amino-terminal domain of the receptor. Point mutations and deletions in the androgen receptor gene cause androgen insensitivity syndrome, however subjects with Kennedy's disease have normal virilization, although progressive gynaecomastia, testicular atrophy and infertility may occur. Androgen receptors are expressed widely in the normal brain, and in the anterior horn cells of the spinal cord; however, their role in neuronal tissue is not known, nor is it known how the androgen receptor gene mutation causes neuronal degeneration. Kennedy's disease is likely to be a 'gain of function' abnormality, so that the presence of the receptor with an increased number of glutamines is toxic to motor neurons. It is possible that the mutation alters interaction of the receptor with other neuronal transcription factors, or neuronotoxicity may occur because of a non-specific effect caused by the presence of a protein with a large homoglutamine domain. Studies of patients with Kennedy's disease have shown that expression of androgen receptor mRNA and protein in spinal cord may be decreased, as can be the affinity of the mutant receptor for androgen. In vitro studies have shown impaired transcription activation ability of the mutant androgen receptor. The age at onset of Kennedy's disease may correlate with the size of the CAG repeat, however there is a large degree of variability of age at onset between subjects with the same number of repeats. Further study of the effect of the Kennedy's disease mutation on androgen receptor function in motor neurons will allow us to increase our understanding of the pathogenesis of this disease.
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PMID:Spinal and bulbar muscular atrophy: androgen receptor dysfunction caused by a trinucleotide repeat expansion. 886 71

A 40-year-old conductor was admitted because of increasing drowsiness and confusion. Two years before admission he had had a first seizure. One year before admission he had a generalized convulsive status epilepticus; the following months he was less able to concentrate. A second status epilepticus was followed by transient weakness of his left arm and a depressed level of consciousness for several weeks. After awakening, he had delusions, and his wife found him demented. In the following months his confusion and drowsiness gradually deteriorated. He had previously had gonorrhoea, an episode of fever and exanthema, and was found to have oligospermia as cause of his infertility. On examination he was disoriented, and he had dysarthria. His left pupil was smaller, but both pupils reacted normally. There was left hemianopia and cerebellar ataxia. CT and MR showed large ventricles and periventricular diffuse lesions in the white matter. CSF examination revealed leucocytosis and increased protein content. Further examination were focussed on serological evidence of syphilis, and finally neurosyphilis was diagnosed. After treatment with penicillin, the patient started to recover.
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PMID:[Clinical judgment and decision making in clinical practice. A music conductor with epilepsy followed by memory disorders]. 921 89