Mitokondriesygdommene MDS og MNGIE’s relation til fejl i enzymerne TK2, dGK og TP: The Mitochondrial Diseases MDS and MNGIE and their Relation to the Enzymes TK2, dGK and TP

Abstrakt

Within the last decade, the enzymes thymidine phosphorylase (TP), thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) have been related to several mitochondrial diseases. Since the millennium this research has been intensified. Through studying literature, we have tried to link specific diseases to certain mutations in the genes encoding the 3 enzymes. This is written as a review article. TK2 and dGK phosphorylate nucleosides to nucleotides, which are then used in the DNA-synthesis in the mitochondria. TP splits thymidine to thymine and deoxyribose-1-phosphate. Through studies we have found that there is a link between mutations in the genes encoding TK2 and dGK to the MDS disease. Inactive TK2 and dGK will result in an insufficient supply of deoxynucleotides, due to a lack of phosphorylation of thymidine and guanosine. Mutations in TK2 cause the myopathic form of MDS while mutations in dGK, causes the hepatocerebral form of MDS. The disease MNGIE (Mitochondrial NeuroGastroIntestinal Encephalomyopathy) is caused by a mutation in the gene encoding the enzyme TP. MNGIE is among other things characterized by weight loss, loss of muscle mass, numbness, loss of reflexes and an attack on the white brainmatter. The enzymes are possibly involved in other combinations than those described above apoptosis, cancer and aging, for instance. Therefore intensive research is required on this subject.