MNGIE is an autosomal recessive disease caused by lossof-function mutations in the ECGF1 gene encoding thymidine phosphorylase (TP)(3, 4). In MNGIE, the severe loss of TP activity (< 10% of mean control TP activity) leads to markedly elevated plasma levels of thymidine and deoxyuridine nucleosides and also mtDNA alterations (4). We have identified 85 MNGIE patients with this unique combination of genetic and biochemical alterations indicating that the ECGF1 mutations are indeed pathogenic (Hirano, unpublished observation). We have hypothesized that high concentrations of pyrimidine nucleosides cause nucleotide pool imbalance, which leads to impaired mtDNA replication, repair, or both (4).