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)

Two sisters in the first year of life presented with a proximal tubulopathy of unknown etiology. They subsequently developed a pluritissular disorder including diabetes mellitus, skin abnormalities, mitochondrial myopathy with ragged-red fibers, and cerebellar ataxia. Their mother had ptosis, ophthalmoplegia, and muscle weakness. Analysis of the mitochondrial respiratory chain showed a complex III deficiency in both skeletal muscle and lymphocytes of the second girl. Southern blot analysis provided evidence for a heteroplasmic partial duplication of the mtDNA (26 kb), involving one full-length and one partly deleted mitochondrial genome and with one single abnormal junction between the genes for ATPase 6 and cytochrome b. Using PCR amplification of lymphocyte DNA, we were able to detect minute amounts of duplicated molecules in the mother, which provided evidence for maternal inheritance of the partial duplication. While maternal transmission of point mutations have been reported in Leber disease, retinitis pigmentosa, and MERRF disease, this observation is, to our knowledge, the first example of a maternally inherited duplication of the mitochondrial genome in man.
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PMID:Maternally inherited duplication of the mitochondrial genome in a syndrome of proximal tubulopathy, diabetes mellitus, and cerebellar ataxia. 153 Nov 67

A 19-year-old man born with thyroprivic hypothyroidism, due to congenital development defect, manifested hypogonadism, stunted growth, chronic progressive external ophthalmoplegia (CPEO), diffuse muscle weakness and wasting, right bundle branch block, cerebral atrophy. Muscle biopsy showed mitochondrial abnormalities. Biochemical investigations on muscle disclosed partial (50%) cytochrome c oxidase deficiency, 58% decrease of cytochrome aa3 and 41% decrease of cytochrome b. Enzyme-linked immunosorbent assay showed decrease of the immunologically active enzyme protein.
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PMID:Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency. 254 Feb 84

A 32-year-old woman developed chronic progressive hearing impairment, trunkal ataxia, bilateral ptosis and external ophthalmoplegia. She also showed slowly progressive mild to moderate proximal dominant muscle weakness and atrophy. ECG showed incomplete right bundle branch block. An aerobic exercise test showed abnormal blood lactate elevation and muscle biopsy revealed ragged-red fibers in addition to the myopathic change. Analysis of mitochondrial DNA extracted from biopsied muscle and fibroblast samples revealed a 1,758bp deletion from the cytochrome b to ND6 coding regions. Common mutations in tRNALeu(UUR) coding region to the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) were not present. She was diagnosed as having incomplete Kearns-Sayre syndrome (KSS). Since the age of 35, she developed complex partial seizure attacks with secondary generalization frequently and at the age of 42, she had a severe generalized seizure with delayed consciousness loss followed by left hemiplegia. MRI showed wide T2-high signal lesions in the right temporo-parieto-occipital area. The proton MR-spectroscopy showed prominent increase of lactate beyond the lesions detected by MRI, indicating diffuse aerobic metabolic dysfunction in the central nervous system. We reviewed two other KSS cases with a stroke like episode, who also had epilepsy and large deletion but no tRNALeu(UUR) mutation, in mitochondrial DNA. Patients with KSS who have seizure may develop the stroke-like episode as seen in MELAS patients.
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PMID:[A case of incomplete Kearns-Sayre syndrome with a stroke like episode]. 940 43

Kearns-Sayre syndrome (KSS) is a progressive neuromuscular disease characterized by ophthalmoplegia, cardiac conduction block, and pigmentary retinopathy associated with abnormal mitochondrial structure and function. Usually mitochondrial DNA (mtDNA) deletions have been associated with Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia. Size and position of the deletions differ markedly among these patients. The present study confirms this observation for a patient with KSS by a muscle and nerve biopsy in which we detected a 1.2 kb mtDNA deletion. The location of the deletion, however, is unusual in this case: its position comprises nucleotides 14952 to 15739. The defect is heteroplasmic and concerns the cytochrome b and tRNA genes. Complex I and IV of the respiratory chain were intact in this case, indicating that below a threshold of tRNA formation, the impaired biosynthesis and membrane integration of one respiratory complex may cause the phenotypical appearance of the KSS syndrome associated with a subclinical neuropathy.
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PMID:Mitochondrial cytochrome b gene deletion in Kearns-Sayre syndrome associated with a subclinical type of peripheral neuropathy. 983 55

A 33-year-old Japanese man had Kearns-Sayre syndrome (KSS), which consists of the triad of external ophthalmoplegia, heart block, and "salt-and-pepper" retinopathy. The other systemic manifestations included sensorineural hearing loss, slight generalized muscle weakness, cerebellar ataxia, and elevated levels of cerebrospinal fluid protein. He exhibited a heteroplasmic mitochondrial DNA deletion of approximately 9 kb between the cytochrome c oxidase subunit 1 and cytochrome b genes. In the authors' experience, this deletion is one of the longest to be observed in such patients. His fundi were characterized bilaterally by white flecks in the inner layers of retina at the midperiphery. Visual evoked potentials showed delayed latency in the P100 component. The tibial somatosensory evoked potential revealed a marked prolongation of interpeak latency between the N20 and P40 components. Brain magnetic resonance images revealed high-intensity foci in several regions on T2-weighted images. Electrophysiological and magnetic resonance imaging findings suggested an involvement of the white matter of the central nervous system in this patient that was not reflected in the clinical findings.
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PMID:Patient with Kearns-Sayre syndrome exhibiting abnormal magnetic resonance image of the brain. 985 14

We compared the distribution of deleted mitochondrial DNA (Delta-mtDNA) in skeletal muscle of a patient with autosomal recessive (AR) and another with autosomal dominant (AD) progressive external ophthalmoplegia (PEO) by in situ hybridization (ISH). The patients studied had similar numbers of fibers deficient in cytochrome c oxidase (COX) activity (13.6% and 12.8%) and fibers with mitochondrial proliferation (5.5% and 5.3%). ISH suggested that each COX-deficient fiber contained a single species of Delta-mtDNA. Most deletions ablated the region between the genes encoding adenosine triphosphate (ATP) synthase subunit 8 and cytochrome b. Fibers that appeared to be depleted of mtDNA were also present. We conclude that muscle from patients with autosomally inherited PEO contains not only Delta-mtDNA but also focal depletion of mtDNA and that the distribution of these mtDNA defects appears to be similar. These changes most likely represent the common consequence of whatever genetic factors are responsible for the generation of Delta-mtDNA.
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PMID:Analysis of mtDNA deletions in muscle by in situ hybridization. 1059 Apr 9

We report a previously undescribed 7676 base pair mitochondrial (mt)DNA deletion involving genes of complex I, complex IV subunits 2 and 3 (cytochrome oxidase [Cox] II, III), adenosine triphosphatase 8 and 6, cytochrome b and 8 transfer (t)RNA genes producing myopathy and progressive external ophthalmoplegia (PEO) in a 44-year-old right-handed Caucasian man with features of multiple sclerosis (MS). We performed complete mtDNA sequencing and deletion analysis, spectrophotometric analysis of muscle and platelet respiratory chain activity, measurement of platelet mitochondrial membrane potential with the potentiometric dye JC-1 and magnetic resonance spectroscopy (MRS) and MRI studies of normal-appearing and lesional cerebral tissue. The deletion resulted in significant respiratory chain deficiency in muscle and blood and abnormalities of the platelet mitochondrial membrane potential. However, cerebrospinal fluid analysis, magnetic resonance spectroscopy and MRI features suggested inflammatory central nervous system demyelination rather than a primary respiratory chain disorder. We conclude that this novel mtDNA deletion causing myopathy and PEO is associated with severe muscle and platelet cellular energetic abnormalities. Furthermore, clinical and paraclinical features of multiple sclerosis were found. The potential pathomechanistic interaction between mtDNA variation and multiple sclerosis is reviewed.
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PMID:A novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis. 2179 50