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)

We report a 61-year-old, right-handed woman with motor neuron disease, dementia, and apraxia of the upper limbs. The patient developed clumsiness of the right hand and dysarthria two years and a half prior to admission. Neurological examination showed limb-kinetic apraxia and ideomotor apraxia, predominantly on the right side, in addition to dementia and anarthria. There was mild muscle wasting in the neck and hands. A muscle biopsy from the biceps muscle of arm as well as needle EMG revealed neurogenic changes compatible with motor neuron disease. Brain MRI indicated pyramidal tract degeneration. Three-dimensional brain perfusion imaging generated from SPECT demonstrated an asymmetric decrease in cerebral blood flow in the fronto-temporo-parietal regions, predominantly on the left side. This case suggests that asymmetric limb apraxia can be associated with motor neuron disease.
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PMID:[A case of motor neuron disease with dementia and apraxia of the upper limbs]. 1273 88

We report a 70-year-old woman with bilateral optic atrophy, external ophthalmoplegia, bilateral blepharoptosis, and sensory ataxic neuropathy. She had a visual disturbance since childhood. She had dysarthria and gait disturbance at 28 years old. She had bilateral blepharoptosis, marked gait disturbance and dysphagia at 50. On neurological examination, external ophthalmoplegia, bilateral blepharoptosis, mild weakness and muscular atrophy of promixal muscles, hyporeflexia, positive Romberg sign, glove and stocking type sensory disturbance including hypesthesia, hypalgesia, and bathyhypesthesia were found. She did not show pigmented retinopathy, cognitive dysfunctions, hearing loss, cerebellar ataxia, Hoffman reflex nor Babinski sign. She did not show increased lactic acid nor pyruvic acid in the cerebrospinal fluid but mild increase of pyruvic acid (1.0 mg/dl) in her serum. The conduction velocity and amplitude of CMAP of tibial nerve was 37.4 m/sec and 2.9 mV, respectively. The SNAP of ulner and sural nerve were not evoked. Brain MRI showed no pathological findings. Muscle biopsy from the biceps muscle showed many ragged-red fibers (5.3%) and some fibers with decreased or absent COX activity. Sural nerve biopsy showed a marked loss of large myelinated fibers with thin myelinated fibers, and onion-bulb formation. The clinical findings of our patient is similar to that of SANDO (the triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis), however, large mtDNA deletion reported by Fadic in patients with SANDO was not found in our patient. It might be possible that her mtDNA deletion is small or point mutation is existed.
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PMID:[A case of mitochondrial myopathy with external ophthalmoplegia and ataxic neuropathy]. 1472 65

Senataxin recently was identified as the mutated gene in ataxia-oculomotor apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased alpha-fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10 French-Canadian families. All cases have a homogeneous phenotype consisting of a progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and motor neuropathy, and increased alpha-fetoprotein levels but absence of oculomotor apraxia. Linkage disequilibrium was observed with markers in the ataxia-oculomotor apraxia 2 locus on chromosome 9q34. We have identified four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T-->G mutation changes the leucine encoded by codon 1976 to an arginine in the helicase domain (L1976R), and the 193G-->A mutation changes a glutamic acid encoded by codon 65 into a lysine in the N-terminal domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20 (85%) carrier chromosomes. The study of this large French-Canadian cohort better defines the phenotype of this ataxia and presents two novel mutations in senataxin including the more common founder mutation in the French-Canadian population.
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PMID:Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. 1573 1

Spinobulbar muscular atrophy (SBMA) is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria and mild androgen insensitivity. SBMA is caused by CAG repeat expansion in the androgen receptor gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of SBMA (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of SBMA was molecularly confirmed. The ranges are similar to those reported for other populations.
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PMID:CAG repeat polymorphism in the androgen receptor (AR) gene of SBMA patients and a control group. 1587 92

We report a 69-year-old man who developed paralytic poliomyelitis in childhood and then decades later suffered from fatal respiratory failure. Six months before this event, he had progressive weight loss and shortness of breath. He had severe muscular atrophy of the entire right leg as a sequela of the paralytic poliomyelitis. He showed mild weakness of the facial muscle and tongue, dysarthria, and severe muscle atrophy from the neck to proximal upper extremities and trunk, but no obvious pyramidal signs. Electromyogram revealed neurogenic changes in the right leg, and in the paraspinal, sternocleidomastoid, and lingual muscles. There was a slight increase in central motor conduction time from the motor cortex to the lumbar anterior horn. Pulmonary function showed restrictive ventilation dysfunction, which was the eventual cause of death. Some neuropathological features were suggestive of amyotrophic lateral sclerosis (ALS), namely Bunina bodies. In patients with a history of paralytic poliomyelitis who present after a long stable period with advanced fatal respiratory failure, one may consider not only respiratory impairment from post-polio syndrome but also the onset of ALS.
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PMID:Respiratory failure in a patient with antecedent poliomyelitis: amyotrophic lateral sclerosis or post-polio syndrome? 1616 67

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which no curative therapy exists. However, since recent research may provide opportunities for medical treatment, information concerning the natural history of SBMA would be beneficial in planning future clinical trials. We investigated the natural course of SBMA as assessed by nine activities of daily living (ADL) milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2 years; range = 30-87 years) followed from 1 to 20 years. All the patients were diagnosed by genetic analysis. Hand tremor was an early event that was noticed at a median age of 33 years. Muscular weakness occurred predominantly in the lower limbs, and was noticed at a median age of 44 years, followed by the requirement of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed pneumonia at a median age of 62 and 15 of them died at a median age of 65 years. The most common cause of death in these cases was pneumonia and respiratory failure. The ages at onset of each ADL milestone were strongly correlated with the length of CAG repeats in the AR gene. However CAG-repeat length did not correlate with the time intervals between each ADL milestone, suggesting that although the onset age of each ADL milestone depends on the CAG-repeat length in the AR gene, the rate of disease progression does not. The levels of serum testosterone, an important triggering factor for polyglutamine-mediated motoneuron degeneration, were maintained at relatively high levels even at advanced ages. These results provide beneficial information for future clinical therapeutic trials, although further detailed prospective studies are also needed.
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PMID:Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. 1662 16

Hereditary spastic paraplegia describes a diverse group of disorders characterized by progressive paraparesis primarily affecting lower limbs. In Troyer syndrome, an autosomal recessive form of hereditary spastic paraplegia, patients have dysarthria, distal amyotrophy, developmental delay and short stature in addition to spastic paraparesis. It is caused by a frameshift mutation (1110delA) in SPG20 leading to premature truncation of spartin, a protein with no known function. The objective of this study was to determine the subcellular localization of spartin and investigate the effect of the 1110delA mutation. We observed cytoplasmic expression of spartin in all transfected cell lines. Using superimposed organelle markers or immunocytochemistry staining, we established that spartin localizes to mitochondria and that this localization is dependent on sequences in the C-terminal region. Mutant spartin containing the 1110delA mutation has lost mitochondrial localization. Immunocytochemistry staining using anti-alpha-tubulin antibody provided evidence for partial co-localization of spartin with microtubules. Analysis of fluorescence resonance energy transfer indicated that sequences in the amino terminal are important in mediating microtubule interaction. This study provides the first evidence of spartin subcellular localization and identifies it as the third mitochondrial protein implicated in hereditary spastic paraplegia. Our results suggest that Troyer syndrome may be due to defective microtubule-mediated trafficking of mitochondria and/or mitochondrial dysfunction.
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PMID:The hereditary spastic paraplegia protein spartin localises to mitochondria. 1694 7

Like Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which a very defined population of neurons selectively degenerates. Muscular atrophy and central paresis develop in ALS patients relatively quickly--usually within months to a few years. Bulbar symptoms such as swallowing disorders and dysarthria are frequently observed in the beginning. The disease progresses steadily and without remission. The average length of survival after diagnosis is two to three years. The diagnosis is made on the basis of a characteristic group of symptoms and confirmed or substantiated through additional clinical neurological tests. Currently, the cause of the disease cannot be treated. Treatment concentrates primarily on symptomatic measures and providing supportive devices.
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PMID:[Diagnosis and treatment of amyotrophic lateral sclerosis]. 1772 75

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.
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PMID:Sacsinopathies: sacsin-related ataxia. 1785 17

Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous disorders. Both "uncomplicated" and "complicated" forms have been described with various modes of inheritance. Sixteen loci for autosomal-recessive "complicated" HSP have been mapped. The SPG15 locus was first reported to account for a rare form of spastic paraplegia variably associated with mental impairment, pigmented maculopathy, dysarthria, cerebellar signs, and distal amyotrophy, sometimes designated as Kjellin syndrome. Here, we report the refinement of SPG15 to a 2.64 Mb genetic interval on chromosome 14q23.3-q24.2 and the identification of ZFYVE26, which encodes a zinc-finger protein with a FYVE domain that we named spastizin, as the cause of SPG15. Six different truncating mutations were found to segregate with the disease in eight families with a phenotype that included variable clinical features of Kjellin syndrome. ZFYVE26 mRNA was widely distributed in human tissues, as well as in rat embryos, suggesting a possible role of this gene during embryonic development. In the adult rodent brain, its expression profile closely resembled that of SPG11, another gene responsible for complicated HSP. In cultured cells, spastizin colocalized partially with markers of endoplasmic reticulum and endosomes, suggesting a role in intracellular trafficking.
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PMID:Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. 1839 78


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