Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on 7 patients suffering from chronic renal failure (2 females, 5 males; aged 35-75 (phi 53.5) years) who showed severe neuromyeloencephalopathy (NME) after high doses of a new Henle's loop diuretic, Muzolimine. The temporal and phenomenological development of these systems was strikingly parallel. The neurological deficit was revealed on neurophysiological, neuroradiological and in 2 cases on neuropathological tests (gross demyelinisation of the posterior column, mainly of the fasciculus gracilis, less in the lateral corticospinal tract and in some spinal roots). The critical drug dose for first neurological impairment was 52 g on average; at this point the patients had been treated for 78 days. The maximal daily dose was 1.440 mg. Dominant clinical features were pallhypaesthesia, ataxia, signs of peripheral neuropathy in combination with hyperreflexia and progressive para- to tetraspastic paresis. Constellation of symptoms, course of disease and findings of additional investigations, especially those of neuropathology, very much resemble Vitamin B12 deficiency and SMON-(Subacute Myelo Optic Neuropathy) syndrome. The rare entity of Muzolimine-NME is discussed in respect to other endogenous and exotoxic neuromyelopathies. We present the hypothesis of a toxic, partially dialysable metabolite of Muzolimine.
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PMID:[Neuromyeloencephalopathy caused by high-dose muzolimine medication in patients with renal failure]. 215 46

It is suggested that mammalian cells have evolved to respond to methionine deficiency since in such circumstances vital methylation reactions are put at risk, due to decreased levels of S-adenosyl-methionine. Enzymatic changes occurring as a result of decreased methionine, S-adenosylmethionine and S-adenosylhomocysteine, optimize the remethylation of homocysteine to methionine by decreasing homocysteine catabolism and channelling cellular folates into 5-methyltetrahydropteroylglutamate (5-CH3-H4 PteGlu). The latter, in addition to optimising the remethylation cycle, directs the folate cofactors away from purine and pyrimidine biosynthesis and decreases the rate of proliferation of rapidly dividing cells thus reducing competition for methionine incorporation into proteins. Decreased cellular homocysteine, as a result of decreased methionine, would also restrict cell division by decreased conversion of plasma 5-CH3-H4PteGlu into intracellular polyglutamates. Cobalamin deficiency, either nutritional or due to exposure to the Co (I) cobalamin inactivating agent nitrous oxide, prevents the demethylation of 5-CH3-H4PteGlu, which even in the presence of adequate amounts of homocysteine and methionine prevents rapidly proliferating cells from converting enough of the plasma 5-CH3-H4 PteGlu into folylpolyglutamate forms to permit normal DNA biosynthesis and cell replication. This, together with the trapping of the cellular folate cofactors in the 5-CH3-H4PteGlu form, results in megaloblastic changes occurring in tissues such as the marrow. The vital role of the methylation reactions was demonstrated by exposing monkeys to nitrous oxide which inactivated their methionine synthetase. The resultant ataxia and severe demyelination was prevented and diminished by methionine supplementation. When methionine synthetase was similarly inactivated in mice it was shown that while 5-CH3-H4PteGlu enters mammalian cells, it is not converted into a polyglutamyl form and subsequently leaves the cell unmetabolised. In similar experiments in rats methionine was found to have only a small effect in restoring folylpolyglutamate biosynthesis, contrary to previous reports using nutritionally cobalamin deficient animals. It was found that a decrease in the deoxythymidine salvage pathway by methionine, under the experimental conditions used, has led others to the mistaken conclusion that methionine has an 'anti-folate' effect in bone marrow, i.e. that it decreases folate availability for thymidylate synthetase.
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PMID:The role of methionine in the intracellular accumulation and function of folates. 661 25

A case of hereditary transcobalamin II deficiency with neurological involvement is described. The patient presented in early infancy with megaloblastic anaemia and was treated with folinic acid from 6 weeks of age. The diagnosis of transcobalamin II deficiency was not made until he was 2 years old when he showed severely retarded intellectual development, ataxia and pyramidal deficit in the limbs. Following treatment with hydroxocobalamin, his condition has slowly improved but he has remained with a severe neurological deficit. The consequences of vitamin B12 deficiency on neurological development in infancy are discussed.
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PMID:Neurological involvement in hereditary transcobalamin II deficiency. 706 75

The high incidence of megaloblastic anemia observed at our institution (2.1% of hospital admissions) prompted us to analyze the causes of cobalamin and/or folate deficiency in 30 patients admitted during the period 1983-1991 to the Medical Department of Locarno District Hospital. The study population includes 19 women and 11 men with a mean age of 69 years (range 28-91 years). All patients had severe macrocytic anemia (mean hemoglobin 74 +/- 23 g/l, MCV 121 +/- 12 fl), striking megaloblastic changes in aspirated marrow, and an elevated serum level of LDH (2170 +/- 2150 U/l). 19 patients had associated thrombocytopenia, 12 leukopenia and 11 both thrombocytopenia and leukopenia. Treatment led to prompt reticulocytosis and correction of megaloblastic changes in all patients, as well as to nearly complete resolution of the neurologic disorder in a patient with severe spastic ataxia. In 15 patients, megaloblastic anemia was caused by folate deficiency related to alcoholism (n = 6, mean age 55 years) and old age or poverty (n = 9, mean age 73 years). Cobalamin deficiency was present in 9 patients (mean age 69 years); it was due to pernicious anemia in 6 patients and to malabsorption in 2, while the cause remained unexplained in 1. The last patients (mean age 76 years) had deficiency of both cobalamin and folate, related to alcoholism (n = 3) or poverty (n = 3).
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PMID:[Megaloblastic anemia: 30 cases in a district hospital]. 787 99

Acquired copper deficiency presents with a spastic gait and sensory ataxia. Spinal cord magnetic resonance imaging (MRI) in patients with copper deficiency myelopathy may show increased T2 signal, most commonly in the dorsal midline cervical and thoracic cord. These imaging findings may be reversible with normalization of serum copper. The clinical and imaging picture is very similar to the subacute combined degeneration seen in patients with vitamin B12 deficiency. Neuroradiologists should consider this possibility when a long segment of symmetric dorsal spinal cord T2-hyperintensity is identified.
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PMID:Imaging features of copper deficiency myelopathy: a study of 25 cases. 1626 34

The hematologic manifestations of copper deficiency are well known and include anemia and neutropenia. In the past few years, the neurological manifestations of acquired copper deficiency in humans has been recognized, the most common being a myelopathy presenting with a spastic gait and prominent sensory ataxia. The known causes of acquired copper deficiency include prior gastric surgery, excessive zinc ingestion, and malabsorption; however, often the cause is unclear. Hyperzincemia may be present even in the absence of exogenous zinc ingestion. The clinical features and neuroimaging findings are similar to the subacute combined degeneration seen in patients with vitamin B12 deficiency. Copper and vitamin B12 deficiency may coexist. The neurological syndrome may be present without the hematologic manifestations. Copper supplementation resolves the anemia and neutropenia promptly and completely and may prevent the neurological deterioration. Improvement, when it occurs, is often subjective and preferentially involves sensory symptoms. This article describes patients with copper deficiency myelopathy seen at the Mayo Clinic in Rochester, Minn, and reviews the literature on neurological manifestations of acquired copper deficiency in humans.
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PMID:Copper deficiency myelopathy (human swayback). 1703 63

Copper deficiency myelopathy is an important and treatable differential diagnosis of vitamin B12 deficiency, of degenerative diseases presenting with the cardinal sign ataxia, and less often of motor neuron diseases. We report a 30-year-old female who presented with progressive gait disorder and sensory disturbances in her feet. Neurological examination showed tetraparesis with spastic ataxia. Laboratory investigations showed malabsorption, anemia, and leukopenia. Further extensive diagnostic investigations revealed copper deficiency due to malabsorption as the probable cause of the neurological deterioration. After oral copper substitution was started, the progression of her neurological symptoms could be stopped.
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PMID:[Copper deficiency as a treatable cause of myelopathy]. 1827 21

Patients with vitamin B12 deficiency have protean neurological manifestations that are often insidious. Acute onset of cerebellar dysfunction and extrapyramidal manifestations like dystonia and chorea are rather uncommon in adults. We describe a patient who manifested with acute onset of language dysfunction, chorea and ataxia. There was no history of hypertension, diabetes or ischemic heart disease. He had low serum vitamin B12 and elevated serum homocystine levels. He improved dramatically following B12 replacement therapy. Our patient provides insight into the pathophysiological mechanism of this rare manifestation. Further the importance of considering vitamin B12 deficiency, in country like India, where vegetarian food practice is quite common, is being emphasized.
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PMID:Serum vitamin B12 deficiency and hyperhomocystinemia: a reversible cause of acute chorea, cerebellar ataxia in an adult with cerebral ischemia. 1867 79

Vitamin B12 and folate deficiency causing neuropsychiatric and thrombotic manifestations, such as peripheral neuropathy, subacute combined degeneration of cord, dementia, ataxia, optic atrophy, catatonia, psychosis, mood disturbances, myocardial infarction and portal vein thrombosis are well known. This present report highlights an unusual presentation of vitamin B12 deficiency-psychotic disorder, extrapyramidal symptoms in a 12-year-old boy. His symptoms responded to parenteral vitamin B12 therapy. So with this report we emphasized that serum vitamin B12 and folate levels should be measured, especially in those patients who present with other known neuropsychiatric features of vitamin B12 and folate deficiency.
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PMID:Psychotic disorder and extrapyramidal symptoms associated with vitamin B12 and folate deficiency. 1909 95

Pernicious anemia is uncommon in Africa. The purpose of this report is to describe a case of pernicious anemia observed in Madagascar. The revealing manifestation was encephalomyelitis with combined medullar sclerosis that responded favorably to vitamin B12 replacement therapy. Clinical symptoms included paresthesia associated with allodynia of all four extremities and with tetrapyramidal syndrome, medullar ataxia and minor cognitive disturbances ongoing for 5 months. Hemogram testing revealed macrocytic anemia. Serum cobalamin level was low. Anti-intrinsic factor antibody was detected. Spinal cord magnetic resonance imaging showed diffuse high-signal intensity along the posterior spinal cord extending from C1 to C4. Vitamin B12 replacement therapy led to full regression of clinical signs after six weeks. Association of central nervous system involvement with macrocytic anemia suggests vitamin B12 deficiency and pernicious anemia should be suspected. This disease can be considered as a curable form of myelitis in Africa and Madagascar.
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PMID:[A case of curable encephalomyelitis in a tropical area: pernicious anemia]. 2187 May 65


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