Late-onset MNGIE due to partial loss of thymidine phosphorylase activity.
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.
Martí
Ramon
R
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Verschuuren
Jan J G M
JJ
Buchman
Alan
A
Hirano
Ikuo
I
Tadesse
Saba
S
van Kuilenburg
André B P
AB
van Gennip
Albert H
AH
Poorthuis
Ben J H M
BJ
Hirano
Michio
M
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
D001120:Arginine; D013939:Thymidine Phosphorylase; D007930:Leucine; D014633:Valine; D005998:Glycine