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Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a mitochondrial DNA depletion disease that has multiple clinical effects including severe gastrointestinal dismotility, cachexia, peripheral neuropathy, and leukoencephalopathy. It is caused by mutations in TYMP, the gene encoding thymidine phosphorylase, and leads to a build up of thymidine. The thymidine level can be measured clinically when MNGIE is suspected in a patient.

Gonzalez-Vioque et al. recently described work in which they showed that increased levels of TTP lead to a secondary dCTP depletion, and this secondary dCTP depletion was the cause of the mtDNA depletion (rather than the excess of TTP itself). They propose that limited dNTP availability is the ultimate cause of mtDNA depletion in this syndrome. This has interesting implications for treatment targets in the treatment of this, and other mtDNA depletion syndromes. (PLOS Genet 2011 Mar;7(3))

Hilary Vernon, MD PhD

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