caa a22 4500 378879359 CHVBK 20180305123428.0 cr unu---uuuuu 161128e20030721xx s 000 0 eng 10.1515/CCLM.2003.128 doi (NATIONALLICENCE)gruyter-10.1515/CCLM.2003.128 Alteration of Nucleotide Metabolism: A New Mechanism for Mitochondrial Disorders [Elektronische Daten] [Ramon Martí, Yutaka Nishigaki, Maya R. Vilá, Michio Hirano] Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP). TP deficiency alters the metabolism of the nucleosides thymidine and deoxyuridine, which, in turn, produces abnormalities of mitochondrial DNA (mtDNA) including depletion, deletions, and point mutations. MNGIE is the best characterized of the expanding number of mitochondrial disorders caused by alterations in the metabolism of nucleosides/nucleotides. Because mitochondria contain their own machinery for nucleoside and nucleotide metabolism and have physically separate nucleotide pools, it is not surprising that disorders of these pathways cause human diseases. Other diseases in this group include mtDNA depletion syndromes caused by mutations on the nuclear genes encoding the mitochondrial thymidine kinase and deoxyguanosine kinase; autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA due to mutations in the genes encoding the muscle-isoform of mitochondrial ADP/ATP translocator; and mitochondrial DNA depletion due to toxicities of nucleoside analogues. Mutations in the deoxynucleotide carrier, a transporter of deoxynucleoside diphosphates, have been identified as a cause of congenital microcephaly. However, alterations of mtDNA have not yet been established in this disorder. Future studies are likely to reveal additional diseases and provide further insight into this new subject. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Medical equipment & techniques nationallicence Medical diagnosis nationallicence Diseases & disorders nationallicence Martí Ramon aut Nishigaki Yutaka aut Vilá Maya R. aut Hirano Michio aut Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/7(2003-07-21), 845-851 1434-6621 41:7<845 2003 41 cclm https://doi.org/10.1515/CCLM.2003.128 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/CCLM.2003.128 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Martí Ramon aut NATIONALLICENCE 700 1- Nishigaki Yutaka aut NATIONALLICENCE 700 1- Vilá Maya R. aut NATIONALLICENCE 700 1- Hirano Michio aut NATIONALLICENCE 773 0- Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/7(2003-07-21), 845-851 1434-6621 41:7<845 2003 41 cclm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter