fig1

Figure 1. Molecular defect in MNGIE. Pathogenic mutations in the nuclear TYMP gene leads to a deficiency in TP activity, resulting in a plasma and cytosolic accumulation of the enzyme’s substrates, thymidine and 2’-deoxyuridine. This leads to imbalances in the mitochondrial deoxyribonucleotide pools (dTTP and dUTP) and ultimately impaired mtDNA repair. TP: thymidine phosphorylase; MNGIE: mitochondrial neurogastrointestinal encephalomyopathy; mtDNA: mitochondrial DNA