title: Late-onset MNGIE due to partial loss of thymidine phosphorylase activity.
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the gene encoding thymidine phosphorylase (TP). All MNGIE patients have had severe loss of TP function and prominent plasma accumulations of the TP substrates thymidine (dThd) and deoxyuridine (dUrd). Here, we report for the first time to our knowledge three MNGIE patients with later onset, milder phenotype, and less severe TP dysfunction, compared with typical MNGIE patients. This report demonstrates a direct relationship between the biochemical defects and clinical phenotypes in MNGIE and supports the notion that reduction of dThd and dUrd accumulation or TP replacement could be useful therapy for MNGIE.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Martí
authors.forename: Jan J G M
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: Alan
authors.initials: A
authors.lastname: Buchman
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hirano
authors.forename: Saba
authors.initials: S
authors.lastname: Tadesse
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: Albert H
authors.initials: AH
authors.lastname: van Gennip
authors.forename: Ben J H M
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D001120:Arginine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017124:Conserved Sequence; D005260:Female; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology* / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000378:metabolism
chemical_list: D001120:Arginine; D013939:Thymidine Phosphorylase; D007930:Leucine; D014633:Valine; D005998:Glycine