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)

Subacute necrotizing encephalomyelopathy (Leigh's syndrome) is a rare neurodegenerative disease in the adult. The precise metabolic defect is unknown, but abnormalities of a mitochondrial enzyme system related to cytochrome-c oxidase or pyruvate dehydrogenase are described. The clinical picture usually consists of an altered breathing pattern, oculomotor paralysis, other signs of cranial nerve dysfunction, ataxia, myoclonic jerks, nystagmus, generalized seizures, optic atrophy and demyelinating peripheral neuropathy. Hypopnea leads to CO2-retention with consecutive loss of consciousness demanding mechanical ventilation. Respiratory failure is the most frequent cause of death. Here we describe two patients with adult onset Leigh's syndrome and we discuss the longterm treatment strategies including vitamin B1 and CPAP mask.
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PMID:[Adult Leigh syndrome. A rare differential diagnosis of central respiratory insufficiency]. 771 56

A 6-month-old female infant was diagnosed with Leigh syndrome after an abnormal muscle specimen was obtained and after magnetic resonance imaging demonstrated characteristic cranial lesions. She presented with episodic hyperventilation, myoclonus, ophthalmoplegia, hypotonia, and elevation of lactate in the cerebrospinal fluid and blood. A series of cranial ultrasounds revealed progressive ventricular enlargement before the typical lesions were detected by magnetic resonance imaging. Myelin destruction is believed to play an important role in the early stage of Leigh syndrome. Ultrasonography may provide a convenient way to document changes in brain that provide early suspicion of Leigh syndrome.
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PMID:Leigh syndrome with progressive ventriculomegaly. 806 Apr 29

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.
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PMID:Clinical manifestation of mitochondrial diseases in children. 821 54

The levels of mitochondrial electron transport system proteins cytochrome c oxidase (COX) and complex III were measured in muscle fibers of patients with mitochondrial encephalomyopathy using quantitative immunoelectron microscopy. In a patient with Leigh's encephalopathy, immunoreactive COX protein was decreased to 20% of the normal mean value in all muscle fibers examined, while the amount of complex III was within the normal range. In a patient with fatal infantile COX deficiency, the level of COX protein was found to be decreased to 27-40% of the normal value in all muscle fibers examined. In patients with mitochondrial myopathy, encephalopathy, lactic acidosis associated with stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO), COX protein levels were decreased to 20% of normal in muscle fibers lacking COX activity. In normal fibers, however, COX protein levels were also normal. The amount of complex III protein was normal in COX-deficient muscle fibers. In two patients, in situ hybridization was performed for detection of mitochondrial mRNA. Mitochondrial mRNAs were found to be abundant in muscle fibers with decreased COX protein, suggesting a defect at the mitochondrial protein-synthesis level in a COX-deficient muscle fiber.
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PMID:Quantitative evaluation of electron transport system proteins in mitochondrial encephalomyopathy. 838 96

Microphotometric enzyme assay was used to study cytochrome c oxidase activity in single human skeletal muscle fibers. The assay techniques combine the precise localization of enzyme activity provided by histochemical methodology with the precise quantitation of a sensitive assay system. Abnormalities of cytochrome c oxidase were investigated using microphotometric enzyme assay in 12 patients with Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, or Leigh's syndrome. Control values were obtained using muscle biopsy specimens from 20 juvenile and 18 adult subjects with no evidence of neuromuscular disease. In the patients with Leigh's syndrome due to cytochrome c oxidase deficiency, the abnormality was found to be expressed uniformly throughout the muscle fiber population. In contrast, patients with Kearns-Sayre syndrome or chronic progressive external ophthalmoplegia showed abnormal heterogeneity of cytochrome c oxidase activity. In many cases, extreme degrees of variability were seen, with fibers containing high activity adjacent to fibers with no detectable activity. Mitochondrial DNA analysis showed that most of the patients with Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia had major rearrangements of mitochondrial DNA. It was concluded that the extreme variability of cytochrome c oxidase activity detected using microphotometric enzyme assay was an indicator of a probable abnormality of mitochondrial DNA. Conversely, cytochrome c oxidase defects in muscle which show a homogeneous distribution are more likely to be associated with defects of the nuclear genome.
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PMID:Cytochrome c oxidase activity in single muscle fibers: assay techniques and diagnostic applications. 838 86

The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role.
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PMID:The mitochondrial DNA transfer RNA(Lys)A-->G(8344) mutation and the syndrome of myoclonic epilepsy with ragged red fibres (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA. 851 95

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

Since the first identification in 1988 of pathogenic mitochondrial DNA (mtDNA) mutations, the mitochondrial diseases have emerged as a major clinical entity. The most striking feature of these disorders is their marked heterogeneity, which extends to their clinical, biochemical, and genetic characteristics. The major mitochondrial encephalomyopathies include MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibers), KSS/CPEO (Kearns-Sayre syndrome/chronic progressive external ophthalmoplegia), and NARP/MILS (neuropathy, ataxia, and retinitis pigmentosum/maternally inherited Leigh syndrome) and they typically present highly variable multisystem defects that usually involve abnormalities of skeletal muscle and/or the CNS. The primary emphasis here is to review recent investigations of these mitochondrial diseases from the standpoint of how the complexities of mitochondrial genetics and biogenesis might determine their varied features. In addition, the mitochondrial encephalomyopathies are compared and contrasted to Leber hereditary optic neuropathy, a mitochondrial disease in which the pathogenic mtDNA mutations produce a more uniform and focal neuropathology. All of these disorders involve, at some level, a mitochondrial respiratory chain dysfunction. Because mitochondrial genetics differs so strikingly from the Mendelian inheritance of chromosomes, recent research on the origin and subsequent segregation and transmission of mtDNA mutations is reviewed.
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PMID:Human mitochondrial diseases: answering questions and questioning answers. 977 Feb 97

Clinical and biochemical classifications of mitochondrial disorders have given way to an as yet incomplete genetic classification system based on alterations of the mitochondrial genome, the nuclear genome, or both. The first group includes mitochondrial disorders due to specific mutations of mitochondrial DNA such as the MELAS, MERRF or NARP encephalomyopathies, various conditions involving deafness (non-syndromic or associated with diabetes), Leber's optic neuropathy and a small group of cases of maternally transmitted Leigh's syndrome. All these diseases are transmitted through maternal line. conditions which are usually sporadic are due to deletion or duplication of mitochondrial DNA, and give rise to myopathies, with or without ophthalmoplegia, and to more complex disorders such as Kearns Sayre syndrome are also included. The second group is composed of all the mitochondrial disorders in which the nuclear genes which codify sub-units of mitochondrial DNA contain a genetic defect. This includes most cases of Leigh's syndrome, Alpers polydystrophies, the myoneurogastrointestinal syndrome, Barth's syndrome and Friedreich's disease. Amongst the disorders secondary to defects in communication between the nuclear and mitochondrial genomes is a progressive external ophthalmoplegic form with autosomal dominance which arises secondary to mutations on chromosomes 3 and 10. Further mitochondrial disorders due to faults in the relationship between the two genomes will probably be found in the near future.
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PMID:[Classification of mitochondrial diseases]. 981 May 85

We report an 8-year molecular study of mitochondrial DNA (mtDNA) mutations in patients with mitochondrial diseases in Taiwan. One hundred and seventy-seven patients met the diagnostic criteria of mitochondrial disease and were recruited into the study. The results showed that 32 patients, including 25 with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, one with Kearns-Sayre syndrome (KSS), one with diabetes mellitus and deafness, and five with chronic progressive external ophthalmoplegia (CPEO), harbored the A3243G mtDNA mutation. The A8344G mutation was found in nine patients, all of whom suffered from myoclonic epilepsy and ragged-red fibers (MERRF) syndrome. The G11778A mtDNA mutation was found in 18 of 22 patients with Leber's hereditary optic neuropathy. The T8993C and T8993G mutations were found, respectively, in one and two patients with Leigh syndrome. Large-scale deletions of mtDNA were found in 17 patients with CPEO, one with KSS, one with MELAS, and two with MERRF syndrome. The mtDNA mutations in patients with each of the mitochondrial diseases found in Taiwan were restricted mainly to a single site, while those reported for the same diseases in other ethnic groups occurred in many sites. Furthermore, significant levels of additional mtDNA mutations occurred in some patients with mitochondrial encephalomyopathies. We suggest that these additional (or secondary) mtDNA mutations are generated as a consequence of the preexisting primary mtDNA mutations and may contribute to the age-dependent progressive deterioration characteristic of mitochondrial diseases.
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PMID:Molecular epidemiologic study of mitochondrial DNA mutations in patients with mitochondrial diseases in Taiwan. 1042 Jul


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