Oculogastrointestinal muscular dystrophy

Ionâşescu, Victor

doi:10.1002/ajmg.1320150114

Cited by 40 publications

(18 citation statements)

References 14 publications

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“…malities affect both intestinal smooth muscles and the enteric nervous system. 4,[7][8][9][10]15 Similarly, manometric studies of the gastrointestinal tract have given variable results. Enteric neuropathy was indicated by esophageal aperistalsis with spontaneous contraction in 1 patient 31 and low-amplitude nonpropagated short duration contractions of the striated portion of the esophagus in another patient.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 In 1976, Okamura and associates 6 reported the first case as "congenital oculoskeletal myopathy with abnormal muscle and liver mitochondria." Since then, more than 35 additional individuals with MNGIE have been described, 4,5,[7][8][9][10][11][12][13][14][15][16] with several acronyms: myo-, neuro-, gastrointestinal encephalopathy (MNGIE) 8 ; polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudoobstruction (POLIP) 9 ; oculogastrointestinal muscular dystrophy (OGIMD) 7 ; and mitochondrial encephalomyopathy with sensorimotor polyneuropathy, ophthalmoplegia, and pseudo-obstruction (MEPOP). 17 We have identified mutations in the gene encoding thymidine phosphorylase (TP), located on chromosome 13.32-qter, as the cause of MNGIE.…”

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confidence: 99%

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Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations

et al. 2000

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Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1‐phosphate. We identified 21 probands (35 patients) who fulfilled our clinical criteria for MNGIE. MNGIE has clinically homogeneous features but varies in age at onset and rate of progression. Gastrointestinal dysmotility is the most prominent manifestation, with recurrent diarrhea, borborygmi, and intestinal pseudo‐obstruction. Patients usually die in early adulthood (mean, 37.6 years; range, 26–58 years). Cerebral leukodystrophy is characteristic. Mitochondrial DNA (mtDNA) has depletion, multiple deletions, or both. We have identified 16 TP mutations. Homozygous or compound heterozygous mutations were present in all patients tested. Leukocyte TP activity was reduced drastically in all patients tested, 0.009 ± 0.021 μmol/hr/mg (mean ± SD; n = 16), compared with controls, 0.67 ± 0.21 μmol/hr/mg (n = 19). MNGIE is a recognizable clinical syndrome caused by mutations in thymidine phosphorylase. Severe reduction of TP activity in leukocytes is diagnostic. Altered mitochondrial nucleoside and nucleotide pools may impair mtDNA replication, repair, or both. Ann Neurol 2000;47:792–800

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations

et al. 2000

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“…Myoneurogastrointestinal encephalopathy (MNGIE), also termed polyneuropathy, ophthalmoplegia, leucencephalopathy, intestinal pseudo‐obstruction (POLIP), is a multisystem disorder, first described in 1983 (Ionasescu, 1983). MNGIE is characterized by gastrointestinal dysmotility, manifesting before age 20 years as episodic nausea, vomiting, gastroparesis, progressive intestinal pseudo‐obstruction, abdominal pain, dilation and dysmotility of oesophagus, stomach and small intestine, diarrhoea, and malabsorption with progressive malnutrition, leading to death around 40 years of age.…”

Section: Myoneurogastrointestinal Encephalopathymentioning

confidence: 99%

Mitochondriopathies

Finsterer

2004

Euro J of Neurology

205

158

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Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.

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“…The association of mitochondrial disorders with gastrointestinal dysfunction has been reported in several cases [20,21]. On the basis of the hypothesis that metabolism impairment might be involved in the pathophysiology of gastrointestinal tract disease, we evaluated the activities of mitochondrial respiratory chain complexes in the stomach of rats subjected to an animal model of gastritis induced by IDM.…”

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confidence: 99%

Gastrin-Releasing Peptide Receptor Antagonist or N-acetylcysteine combined with Omeprazol Protect against Mitochondrial Complex II Inhibition in a Rat Model of Gastritis

Rezin¹,

Petronilho²,

Araújo³

et al. 2010

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis.

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Oculogastrointestinal muscular dystrophy

Cited by 40 publications

References 14 publications

Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations

Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations

Mitochondriopathies

Gastrin-Releasing Peptide Receptor Antagonist or N-acetylcysteine combined with Omeprazol Protect against Mitochondrial Complex II Inhibition in a Rat Model of Gastritis

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