Mitochondrial neurogastrointestinal encephalopathy

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Description from OMIM

Mitochondrial DNA depletion syndrome-1 (MTDPS1) is an autosomal recessive progressive multisystem disorder clinically characterized by onset between the second and fifth decades of life of ptosis, progressive external ophthalmoplegia (PEO), gastrointestinal dysmotility (often pseudoobstruction), cachexia, diffuse leukoencephalopathy, peripheral neuropathy, and mitochondrial dysfunction. Mitochondrial DNA abnormalities can include depletion, deletion, and point mutations (Taanman et al., 2009). Genetic Heterogeneity of Autosomal Recessive Mitochondrial DNA Depletion Syndromes Autosomal recessive mitochondrial DNA depletion syndromes are clinically and genetically heterogeneous. See also MTDPS2 (609560), caused by mutation in the TK2 gene (188250); MTDPS3 (251880), caused by mutation in the DGUOK gene (601465); MTDPS4A (203700) and MTDPS4B (613662), both caused by mutation in the POLG gene (174763); MTDPS5 (612073), caused by mutation in the SUCLA2 gene (603921); MTDPS6 (256810), caused by mutation in the MPV17 gene (137960); MTDPS7 (271245), caused by mutation in the C10ORF2 gene (606075); MTDPS8A (612075) and MTDPS8B (see 612075), both caused by mutation in the RRM2B gene (604712); MTDPS9 (245400), caused by mutation in the SUCLG1 gene (611224); MTDPS10 (212350), caused by mutation in the AGK gene (610345); MTDPS11 (615084), caused by mutation in the MGME1 gene (615076); MTDPS12A (617184) and MTDPS12B (615418), both caused by mutation in the SLC25A4 gene (103220); MTDPS13 (615471), caused by mutation in the FBXL4 gene (605654); MTDPS14 (616896), caused by mutation in the OPA1 gene (605290); and MTDPS15 (617156), caused by mutation in the TFAM gene (600438).

Prevalence of clinical parameters (%)

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List of symptoms

Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Leukodystrophy nervous 100 % 10852545 2011-10-22
Gastrointestinal dysmotility digestive 100 % 10852545 2011-10-18
Neuropathy nervous 100 % 10852545 2011-10-10
Ptosis nervous 100 % 10852545 2011-10-10
Ophthalmoplegia nervous 100 % 10852545 2011-10-10
Weight loss multi 100 % 10852545 2011-10-10
Myopathy skeletal 100 % 10852545 2011-10-22
Abdominal pain digestive 94 % 10852545 2012-07-25
Diarrhea digestive 93 % 10852545 2011-10-10
Gastrointestinal dysmotility digestive 83 % 8164833 2011-10-05
Areflexia nervous 82 % 10852545 2011-10-10
Vomiting digestive 74 % 10852545 2011-10-10
Lactate accumulation circulatory 63 % 10852545 2011-10-22
Hearing loss nervous 45 % 10852545 2011-10-10
Retinitis pigmentosa nervous 6 % 10852545 2011-10-10
Mental retardation nervous 3 % 10852545 2011-10-10

List of references:

Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations.
I Nishino, A Spinazzola, A Papadimitriou, S Hammans, I Steiner, C D Hahn, A M Connolly, A Verloes, J GuimarĂ£es, I Maillard, H Hamano, M A Donati, C E Semrad, J A Russell, A L Andreu, G M Hadjigeorgiou, T H Vu, S Tadesse, T G Nygaard, I Nonaka, I Hirano, E Bonilla, L P Rowland, S DiMauro, M Hirano,

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 micromol/hr/mg (mean +/- SD; n = 16), compared with controls, 0.67 +/- 0.21 micromol/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.

Annals of neurology - Jun 2000

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder.
M Hirano, G Silvestri, D M Blake, A Lombes, C Minetti, E Bonilla, A P Hays, R E Lovelace, I Butler, T E Bertorini,

We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a sensorimotor neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.

Neurology - Apr 1994