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)

An Italian pedigree including two sisters and their mother affected by a neuro-ophthalmic disease characterised by retinitis pigmentosa, ataxia, and psychomotor retardation is reported. Molecular analysis of mitochondrial DNA showed the presence of heteroplasmic 8993 point mutation in the subunit 6 of the ATPase gene. The clinical features and genetic findings in this family were comparable with those recently described in an English family. The mitochondrial DNA analysis of the family showed a correlation between the amount of mutated DNA and the disease severity in the probands, and indicated the presence of a threshold amount of mutated genome inducing ophthalmic defects. Moreover, the comparative analysis of blood, hairs, muscle, and urinary tract epithelia of two probands revealed an essentially similar distribution of mutated and wild type mitochondrial genomes. Our results suggest that the 8993 mitochondrial DNA mutation characterises a disease with similar clinical features in different populations.
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PMID:Retinitis pigmentosa, ataxia, and mental retardation associated with mitochondrial DNA mutation in an Italian family. 843 24

The mitochondrial ATPase 6 gene encodes a subunit of F1F0 adenosine triphosphate (ATP) synthase. A mutation in the ATPase 6 gene has been genetically linked to two maternally inherited genetic diseases: neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) and certain cases of subacute necrotizing encephalopathy (SNE). Although the severity of both NARP and SNE disease were correlated with the quantity of the ATPase 6leu156-->arg mutation in each patient, the mutation could not be shown to alter F1F0-ATP synthase activity. To investigate the biochemical effects of the ATPase 6leu156-->arg mutation on F1F0-ATP synthase, the aleu207-->arg mutation was constructed in the F1F0-ATP synthase from Escherichia coli to serve as a model for the disease mutation. Characterization of the model bacterial enzyme revealed that the mutation abolishes detectable ATP synthesis via oxidative phosphorylation. The aleu207-->arg mutation results in a structural perturbation blocking proton translocation through F1F0-ATP synthase. The results suggest that a structural defect in human F1F0-ATP synthase is the biochemical basis for NARP and SNE.
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PMID:The aleu207-->arg mutation in F1F0-ATP synthase from Escherichia coli. A model for human mitochondrial disease. 850 61

Refsum's disease, firstly described almost 50 years ago by the Norvegian neurologist Sigvald Refsum, is an autosomic recessive disease affecting mostly the Scandinavians and the populations originating from Northern Europe. The disease results from a specific enzyme deficiency of the first step of phytanic acid catabolism pathway. This deficiency leads to an accumulation of this C20 fatty acid in the serum and the tissues with a preference for adipose tissue, liver and kidneys. The clinical picture includes retinitis pigmentosa, peripheral neuropathy, ataxia and elevated cerebrospinal fluid protein concentration. Other less frequent manifestations include cranial nerves deficiency, myocardiopathy, renal tubular dysfunction and ichtyosis. The diagnosis relies on serum phytanic acid measurement. The treatment consists of a phytanic-acid free diet sometimes associated with plasmapheresis. This treatment is generally effective on neuropathy but not on cranial nerves dysfunction and retinitis pigmentosa.
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PMID:[Refsum disease]. 876 99

We present here a report on a 5-year experience in clinical investigation, diagnostic management and molecular genetic studies of neuromitochondrial disorders, defined on the basis of morphological, biochemical and genetic findings. Leigh disease is the most frequent clinical presentation in infancy and childhood, but symptoms at onset are poorly informative. In paediatric cases, lactic acidosis and neuroradiological abnormalities are frequent, and can be of help for the diagnostic orientation. In the adult population, muscle weakness, ophthalmoplegia with ragged-red fibres, retinitis pigmentosa, progressive myoclonal ataxia, and early-onset stroke-like episodes, are frequently combined in complex syndromes that are often familial (maternally inherited) and/or associated with well-established mutations in mitochondrial DNA (mtDNA). However, the presence of overlap syndromes and features common to many neuromitochondrial diseases can complicate the clinical evaluation and the diagnostic approach. The pathogenicity of a given mtDNA mutation can frequently be ascertained by correlating the degree of heteroplasmy with the clinical or biochemical phenotypes. Moreover, transmitochondrial cybrids can be used to test the effects of either mitochondrial or nuclear gene abnormalities in a fully controlled, user-friendly and highly informative system.
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PMID:Neurological presentations of mitochondrial diseases. 888 74

Refsum's disease is an autosomal recessive disease caused by defective alpha-oxidation of phytanic acid. The usual clinical presentation is the association of retinitis pigmentosa, ataxia and chronic severe sensorimotor polyneuropathy. A case of mild purely sensory neuropathy in a 40-year-old patient associated to high CSF protein level led to the diagnosis of Refsum's disease. The paucity of sensory symptoms and signs of neuropathy contrasted with severe reduction of motor and sensory nerve conduction velocities and markedly signs of sensory neuropathy observed in the nerve biopsy. Typical ring-scotomas, retinitis pigmentosa, anosmia, deafness, and high plasma phytanic acid level were present in extensive examination. There was no other case in the family.
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PMID:[Pauci-symptomatic sensory polyneuropathy in Refsum's disease]. 894 45

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

To obtain a better molecular definition of patients with syndromic retinitis pigmentosa, we screened for mitochondrial DNA (mtDNA) alterations of the two ATPase genes and 22 tRNA-coding sequences in 10 patients whose features resembled NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. In two patients, one of whom showed features mimicking Kearns-Sayre syndrome, we identified a heteroplasmic T8993G mutation (average 80%) in the mitochondrial ATPase 6 gene. There was no mutated mtDNA in muscle and leukocytes from the mother of one patient or in leukocytes from his brother, suggesting a rapid segregation of the mutated nucleotide. MtDNA analysis should be considered in the differential diagnosis of patients with syndromic retinitis pigmentosa.
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PMID:Heterogeneous clinical presentation of the mtDNA NARP/T8993G mutation. 922 7

A 23-year-old woman with the mitochondrial encephalomyopathy NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) presented with symptoms of obstructive sleep apnea (OSA). An overnight polysomnogram (PSG) showed apnea, EEG slowing, and a paucity of sleep spindles. The patient had a tracheostomy for OSA, and 5 months later she had normal EEG patterns and marked clinical improvement. We propose that patients with mitochondrial encephalomyopathies should have sleep evaluations if the history suggests OSA.
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PMID:Polysomnographic findings in a patient with the mitochondrial encephalomyopathy NARP. 940 76

Rapid progress has been made in the identification of mitochondrial DNA mutations which are typically associated with diseases of the nervous system and muscle. The well established mitochondrial disorders are maternally inherited and males and females are equally affected. An exception is Leber's hereditary optic atrophy (LHON) which is observed much more frequently in males than in females. There are three common point mutations in LHON which can be homoplasmic or heteroplasmic. In mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) most mutations are single base changes and lie within the tRNA-Leu gene. Point mutations in myoclonic epilepsy with ragged red fibres (MERRF) usually occur within the tRNA-Lys gene but mutations of the tRNA-Leu gene are also observed. MELAS and MERRF mutations are heteroplasmic and there is considerable clinical overlap between these diseases. Point mutations within the ATPase6 gene result in either neuropathy, ataxia and retinitis pigmentosa (NARP) or in Leigh's syndrome. The latter occurs if the mutation is present in the majority of mitochondria (extreme heteroplasmy). Finally, mitochondrial DNA deletions are the cause underlying Kearns-Sayre syndrome (KSS). Apart from the well-established mitochondrial diseases, there is increasing evidence that mitochondrial mutations may also play a role in the neurodegenerative disorders Parkinson, Alzheimer and Huntington disease. The complex I defect found in Parkinson disease is especially interesting in this respect. However, no causative mitochondrial mutation has as yet been established in any of these three common disorders.
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PMID:Recent developments in the molecular genetics of mitochondrial disorders. 951 82

We herein describe a male patient who died at 37 years of age, after having suffered from a slowly progressive syndrome of chronic sensory motor neuropathy, deafness, retinitis pigmentosa and ataxia. The neuropathological study showed symmetric areas of necrosis and demyelination affecting the cerebellum and brainstem. The type of lesion was consistent with the characteristics of Leigh Syndrome. On the basis of the histology of the lesions, we believe that they appeared only a few months before the death of the patient. We underline the atypical clinical picture and suggest that, in certain cases, brain MRI may not be a reliable diagnostic tool.
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PMID:Juvenile Leigh syndrome with protracted course presenting as chronic sensory motor neuropathy, ataxia, deafness and retinitis pigmentosa: a clinicopathological report. 956 72


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