Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sensory ataxia as the chief manifestation of acute neuropathy is rather rare. Of the 224 cases of acute polyneuropathy seen over 6 years (1984-1990) only 10 patients (M:F 3:7) had disabling ataxia as the presenting feature. Their ages ranged from 14-61 years. Antecedent febrile illness was present in 6 patients and the peak deficit evolved over 2-25 days. Severe ataxia, paresthesia, distal areflexia and predominant joint sense loss were common to all, motor weakness was either absent or insignificant. CSF was acellular and revealed elevated protein in 3 subjects. All patients had electrophysiological evidence of severe sensory neuropathy with mild or no motor neuropathy. Sural nerve biopsy in one patient showed loss of large, as well as small, diameter myelinated fibres, secondary demyelination, but no evidence of inflammation. At follow up marginal to moderate improvement in ataxia was noted in only 5 patients. Absence of ophthalmoplegia and motor weakness, poor prognosis and characteristic electrophysiological and histopathological observations suggest that acute ataxic neuropathy may be a distinct entity.
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PMID:Acute ataxic neuropathy: a clinical, electrophysiological and morphological study. 166 83

A woman in her early 60s presented to our Movement Disorders Centre with a 5-year history of progressive peripheral neuropathy, gait instability with falls, blurred vision, cognitive impairment and tremors. The patient was found to have profound sensory ataxia, chronic ophthalmoplegia, dementia with significant deficits in registration and construction and bilateral resting tremor of the hands. Investigations revealed an unremarkable MRI of the brain, negative cerebrospinal fluid studies, and unremarkable chemistries. Nerve conduction studies found a severe sensorimotor axonal polyneuropathy. Genetic testing revealed a compound heterozygous mutation in the POLG1 gene consistent with the diagnosis of Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome.
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PMID:Diagnostic challenges in movement disorders: Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome. 2399 76

Mutations in the nuclear gene POLG (encoding the catalytic subunit of DNA polymerase gamma) are an important cause of mitochondrial disease. The most common POLG mutation, A467T, appears to exhibit considerable phenotypic heterogeneity. The mechanism by which this single genetic defect results in such clinical diversity remains unclear. In this study we evaluate the clinical, neuropathological and mitochondrial genetic features of four unrelated patients with homozygous A467T mutations. One patient presented with the severe and lethal Alpers-Huttenlocher syndrome, which was confirmed on neuropathology, and was found to have a depletion of mitochondrial DNA (mtDNA). Of the remaining three patients, one presented with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), one with a phenotype in the Myoclonic Epilepsy, Myopathy and Sensory Ataxia (MEMSA) spectrum and one with Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO). All three had secondary accumulation of multiple mtDNA deletions. Complete sequence analysis of muscle mtDNA using the MitoChip resequencing chip in all four cases demonstrated significant variation in mtDNA, including a pathogenic MT-ND5 mutation in one patient. These data highlight the variable and overlapping clinical and neuropathological phenotypes and downstream molecular defects caused by the A467T mutation, which may result from factors such as the mtDNA genetic background, nuclear genetic modifiers and environmental stressors.
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PMID:A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease. 2673 72