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)

Patients with cystic fibrosis (CF) and pancreatic malabsorption frequently have vitamin E deficiency. Affected patients may develop spinocerebellar degeneration with dysarthria, ataxia, proximal weakness, proprioceptive loss and areflexia. Of a highly selected group of 10 patients with vitamin E levels below 5 micrograms/ml (normal 5-20 micrograms/ml), 7 had abnormal neurological examinations, predominantly affecting vibration and joint position perception with some severely affected patients manifesting diminished visual acuity, tremor, ataxia and diffuse weakness. Evoked potential studies showed marked abnormalities in 3 patients, demonstrating deficits in the optic pathways and in the cervical cord dorsal column pathways. Evoked potential studies may supplement careful neurological examination in patients with CF before and after supplementation with vitamin E to evaluate their progression and response to treatment.
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PMID:Visual and somatosensory evoked potentials in vitamin E deficiency with cystic fibrosis. 245 91

A 30-year-old woman was thought to have Friedreich's disease because of progressive ataxia, dysarthria, and titubation from age 3 years. Her diet was normal, and there were neither symptoms nor laboratory evidence of liver disease or fat malabsorption. Serum vitamin E content and the ratio of serum vitamin E to total serum lipid were very low, but serum vitamin A, cholylglycine, and lipid levels were normal, as was an oral vitamin E tolerance test. Muscle biopsy showed the lysosomal inclusions of vitamin E deficiency. Mitochondria had normal oxidative phosphorylation using polarographic assays. The cause of her vitamin E deficiency was unknown.
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PMID:Friedreich's disease: V. Variant form with vitamin E deficiency and normal fat absorption. 379 40

A ten-year-old girl had obstructive jaundice in the newborn period which persisted for 4 years despite choledochojejunostomy at 6 weeks. From the age of 6 years she developed a progressive neurological syndrome characterized mainly by dysarthria and ataxia. A causal relationship with her profound vitamin E deficiency seemed likely. Treatment with vitamin E over a 2 1/2 year period appeared to arrest the progression of the neurological deficit and subsequent increase in dosage produced some improvement in her ataxia.
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PMID:Progressive neurological disorder associated with obstructive jaundice and vitamin E deficiency. 713 35

Two adults are described who developed a progressive neurological disorder more than 20 years after the onset of chronic fat malabsorption. The clinical features included dysarthria, cerebellar ataxia, and prominent proprioceptive loss with depressed or absent tendon reflexes. Serum vitamin E was undetectable in both cases. One patient improved clinically and electrophysiologically after oral therapy with vitamin E. The findings in these patients were similar to those in others recently reported with vitamin E deficiency associated with biliary atresia. Electrophysiological observations suggested that the human deficiency state parallels that found neuropathologically in vitamin E-deficient animals.
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PMID:Spinocerebellar degeneration secondary to chronic intestinal malabsorption: a vitamin E deficiency syndrome. 718 49

A 22-year-old man presented with progressive gait instability, tremor, and dysarthria since childhood. Electrophysiologic studies revealed a sensorimotor polyneuropathy. Laboratory studies documented vitamin E deficiency; however, no gastrointestinal, hepatic, or lipoprotein disorder could be identified. Vitamin E therapy normalized the serum level, but there was no neurologic improvement. Isolated vitamin E deficiency, in the absence of lipid malabsorption, should be considered in the evaluation of children and adults with ataxia and peripheral neuropathy.
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PMID:Isolated vitamin E deficiency. 876 Dec 74

The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.
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PMID:Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. 948 73

Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.
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PMID:Acanthocytosis and neurological disorders. 1128 40

Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disease, due to mutations in TTPA gene (Arita et al. in Biochem J 306(Pt. 2):437-443, 1995; Hentati et al. in Ann Neurol 39:295-300, 1996), which encodes for alpha-TTP, a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol. This disease is characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. The neurological symptoms include ataxia, dysarthria, hyporeflexia, and decreased vibration sense, sometimes associated with cardiomyopathy and retinitis pigmentosa (Mariotti et al. in Neurol Sci 25:130-137, 2004). Vitamin E supplementation improves symptoms and prevents disease progress (Doria-Lamba et al. in Eur J Pediatr 165(7):494-495, 2006). Over 20 mutations have been identified in patients with AVED. In the present paper we summarize the recent findings on molecular genetic of this disease including the list of the known mutations.
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PMID:Ataxia with vitamin E deficiency: update of molecular diagnosis. 2046 73

Ataxia due to vitamin E deficiency is important because disease progression can be stopped by supplementary therapy. A limited number of studies and case series suggest that the disease is mainly confined to the cerebellum and spinal cord tract and seems to be more common in North African countries. We report a patient from North Norway with progressive ataxia from the age of 5, bilateral dropfoot, Babinski's sign, dysarthria and early epilepsy. Two mutations, 513insTT and p.Arg134x, were detected. When treatment was initiated 25 years after onset of symptoms, the patient was bound to the wheel chair. No further progression of pareses, ataxia or epileptic seizures has been observed in a 3-year follow-up period. This case indicates that cerebral involvement may be present in patients with a lack of vitamin E. If this observation is confirmed, a further exploration of clinical presentation, anatomic involvement and geographic distribution of the disease is warranted.
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PMID:Epilepsy in a patient with ataxia caused by vitamin E deficiency. 2269 89

Refractory vitamin E deficiency is thought to have irreversible effects on neurologic function. We report an adolescent boy with severe refractory vitamin E deficiency due to progressive familial intrahepatic cholestasis (PFIC) type 2. His consequent neurologic dysfunction included severe ataxia, dysmetria, dysarthria, and cranial nerve VI palsy. He underwent liver transplantation at age 13 due to his neurologic dysfunction; and afterward, he had marked improvement in neurologic function. We demonstrate that in a patient with PFIC 2 and severe refractory vitamin E deficiency, liver transplant can improve vitamin E absorption, prevent further neurological sequelae, and reverse prior neurologic dysfunction.
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PMID:Liver Transplantation as a Treatment for Severe Refractory Vitamin E Deficiency Related to Progressive Familial Intrahepatic Cholestasis Type 2 in a Pediatric Patient. 2811 44


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