TY - JOUR
T1 - Mitochondrial neurogastrointestinal encephalomyopathy
T2 - An autosomal recessive disorder due to thymidine phosphorylase mutations
AU - Nishino, Ichizo
AU - Spinazzola, Antonella
AU - Papadimitriou, Alexandros
AU - Hammans, Simon
AU - Steiner, Israel
AU - Hahn, Cecil D.
AU - Connolly, Anne M.
AU - Verloes, Alain
AU - Guimarães, João
AU - Maillard, Ivan
AU - Hamano, Hitoshi
AU - Donati, M. Alice
AU - Semrad, Carol E.
AU - Russell, James A.
AU - Andreu, Antonio L.
AU - Hadjigeorgiou, Giorgos M.
AU - Vu, Tuan H.
AU - Tadesse, Saba
AU - Nygaard, Torbjoern G.
AU - Nonaka, Ikuya
AU - Hirano, Ikuo
AU - Bonilla, Eduardo
AU - Rowland, Lewis P.
AU - Dimauro, Salvatore
AU - Hirano, Michio
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1002/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y
DO - 10.1002/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y
M3 - Article
C2 - 10852545
AN - SCOPUS:0034096975
SN - 0364-5134
VL - 47
SP - 792
EP - 800
JO - Annals of neurology
JF - Annals of neurology
IS - 6
ER -