Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
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.
Valentino
Maria Lucia
ML
Department of Neurology, Columbia University Medical Center, 630 W. 168th Street, P&S 4-443, New York, NY 10032, USA.
Martí
Ramon
R
Tadesse
Saba
S
López
Luis Carlos
LC
Manes
Jose L
JL
Lyzak
Judy
J
Hahn
Angelika
A
Carelli
Valerio
V
Hirano
Michio
M
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
D013939:Thymidine Phosphorylase; D010100:Oxygen; D013936:Thymidine; D003857:Deoxyuridine