title: Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease due to ECGF1 gene mutations causing thymidine phosphorylase (TP) deficiency. Analysis of post-mortem samples of five MNGIE patients and two controls, revealed TP activity in all control tissues, but not in MNGIE samples. Converse to TP activity, thymidine and deoxyuridine were absent in control samples, but present in all tissues of MNGIE patients. Concentrations of both nucleosides in the tissues were generally higher than those observed in plasma of MNGIE patients. Our observations indicate that in the absence of TP activity, tissues accumulate nucleosides, which are excreted into plasma.
authors.affiliation: Department of Neurology, Columbia University Medical Center, 630 W. 168th Street, P&S 4-443, New York, NY 10032, USA.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Valentino
authors.forename: Ramon
authors.initials: R
authors.lastname: Martí
authors.forename: Saba
authors.initials: S
authors.lastname: Tadesse
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: López
authors.forename: Jose L
authors.initials: JL
authors.lastname: Manes
authors.forename: Judy
authors.initials: J
authors.lastname: Lyzak
authors.forename: Angelika
authors.initials: A
authors.lastname: Hahn
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D001706:Biopsy; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000378:metabolism
chemical_list: D013939:Thymidine Phosphorylase; D010100:Oxygen; D013936:Thymidine; D003857:Deoxyuridine