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)

Many reports of diabetic ophthalmoplegia have been published from the clinical points of view. However, there have been only three autopsied cases in which the ocular nerves were investigated histopathologically. A 72-year-old housewife was diagnosed to have glycosuria at the age of 67, but no medical treatment was done. She admitted to the hospital, because of acute onset of right eyelid drooping and diplopia for previous four days. She showed complete eyelid ptosis, moderate dilatation of right pupil, loss of light reaction, and extraocular muscle palsy except abduction on the right. Blood pressure was normal. A glucose tolerance test was diabetic and HbA1c was moderately increased. Her diabetes was fairly well-controlled with a diet therapy and injection of lente insulin. Two and a half months after admission, the course of illness became regressive. Seven months later, external ophthalmoplegia was disappeared and only slight anisocoria was seen. She readmitted to the hospital one year and eleven months later, because of anorexia and emaciation. She died of adenocarcinoma of the stomach without chemotherapy. The duration from onset of ocular symptoms to death was two years and one month. At postmortem examination, stomach cancer infiltrated extensively to the abdominal and pelvic viscera, but no metastasis to the nervous system or intraorbital tissues was found. There were mild to moderate atherosclerotic changes in the small-and middle-sized arteries of the kidneys, pancreas and adrenal glands corresponding to her age. Moderate atherosclerosis was found in all of the major arteries including Willis ring, siphon of the right internal carotid artery and Vertebro-basilar one.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Diabetic ophthalmoplegia--a clinico-pathological study of the first case in Japan]. 269 31

We investigated endocrine function in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy associated with ragged-red fibers (MERRF), and chronic progressive external ophthalmoplegia (CPEO). Hypothalamic-pituitary function was impaired in all three patients with MELAS or MERRF, but none of four with CPEO. A MELAS patient with dwarfism and impaired adolescent development had decreased growth hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A MERRF patient had emaciation and low adrenocorticotropin. A patient with mitochondrial encephalomyopathy transitional between MELAS and MERRF showed delayed, blunted LH and FSH response to LH-releasing hormone stimulation. We concluded that patients with mitochondrial encephalomyopathies, especially MELAS or MERRF, are likely to have hypothalamic-pituitary dysfunction.
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PMID:Dysfunction of the hypothalamic-pituitary system in mitochondrial encephalomyopathies. 970 89

Known disease mechanisms in mitochondrial DNA (mtDNA) maintenance disorders alter either the mitochondrial replication machinery (POLG, POLG2 and C10orf2) or the biosynthesis pathways of deoxyribonucleoside 5'-triphosphates for mtDNA synthesis. However, in many of these disorders, the underlying genetic defect has yet to be discovered. Here, we identify homozygous nonsense and missense mutations in the orphan gene C20orf72 in three families with a mitochondrial syndrome characterized by external ophthalmoplegia, emaciation and respiratory failure. Muscle biopsies showed mtDNA depletion and multiple mtDNA deletions. C20orf72, hereafter MGME1 (mitochondrial genome maintenance exonuclease 1), encodes a mitochondrial RecB-type exonuclease belonging to the PD-(D/E)XK nuclease superfamily. We show that MGME1 cleaves single-stranded DNA and processes DNA flap substrates. Fibroblasts from affected individuals do not repopulate after chemically induced mtDNA depletion. They also accumulate intermediates of stalled replication and show increased levels of 7S DNA, as do MGME1-depleted cells. Thus, we show that MGME1-mediated mtDNA processing is essential for mitochondrial genome maintenance.
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PMID:Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. 2331 56

We ascertained a child with early onset cerebellar ataxia and identified a novel frameshift deletion, c.359del [p. (Pro120Leufs*2), NM_052865.2] in exon 2 of MGME1 (mitochondrial genome maintenance exonuclease 1) by exome sequencing. Variations in MGME1 have been reported to cause mitochondrial DNA (mtDNA) depletion syndrome 11 (MIM #615084) in an earlier work. The phenotype included progressive external ophthalmoplegia, emaciation, respiratory failure and late onset progressive ataxia. However, the child presented here has early onset progressive ataxia, speech delay, microcephaly, cerebellar atrophy and fundus albipunctatus. This is the second report of a mutation in MGME1 and describes a more severe phenotype.
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PMID:Homozygous c.359del variant in MGME1 is associated with early onset cerebellar ataxia. 2871 39

Mitochondrial nucleases play important roles in accurate maintenance and correct metabolism of mtDNA, the own genetic materials of mitochondria that are passed exclusively from mother to child. MGME1 is a highly conserved DNase that was discovered recently. Mutations in MGME1-coding gene lead to severe mitochondrial syndromes characterized by external ophthalmoplegia, emaciation, and respiratory failure in humans. Unlike many other nucleases that are distributed in multiple cellular organelles, human MGME1 is a mitochondria-specific nuclease; therefore, it can serve as an ideal target for treating related syndromes. Here, we report one HsMGME1-Mn2+ complex and three different HsMGME1-DNA complex structures. In combination with in vitro cleavage assays, our structures reveal the detailed molecular basis for substrate DNA binding and/or unwinding by HsMGME1. Besides the conserved two-cation-assisted catalytic mechanism, structural analysis of HsMGME1 and comparison with homologous proteins also clarified substrate binding and cleavage directionalities of the DNA double-strand break repair complexes RecBCD and AddAB.
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PMID:Structural insights into DNA degradation by human mitochondrial nuclease MGME1. 3024 21