Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency.
OBJECTIVE
To assess alterations in brain metabolites in patients with late-onset ornithine transcarbamylase deficiency (OTCD).


METHODS
Six unrelated, asymptomatic Japanese late-onset OTCD patients were analyzed by proton MRS ((1)HMRS) using a point-resolved spectroscopy technique (repetition and echo times, 5000 and 30 ms). Localized spectra for the centrum semiovale were acquired and absolute metabolite concentrations were calculated using an LCModel.


RESULTS
Compared with age-matched controls, N-acetylaspartate and creatine concentrations were normal in all patients. The glutamine (Gln) plus glutamate concentration was increased in four patients, which progressed in proportion to the clinical stage. myo-inositol (mI) could not be detected in five symptomatic patients. A decreased choline (Cho) concentration was detected in two clinically severe patients. (1)HMRS after liver transplantation in one patient revealed the normalization of all metabolites.


CONCLUSIONS
These findings suggest progression of neurochemical events in OTCD, i.e., mI depletion and Gln accumulation followed by Cho depletion, which is reverse of that in hepatic encephalopathy, i.e., Cho depletion followed by mI depletion and Gln accumulation.
Takanashi
J
J
Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan. jtaka@med.m.chiba-u.ac.jp
Kurihara
A
A
Tomita
M
M
Kanazawa
M
M
Yamamoto
S
S
Morita
F
F
Ikehira
H
H
Tanada
S
S
Kohno
Y
Y
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D016031:Liver Transplantation; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D011522:Protons
D011522:Protons; D005973:Glutamine; D007294:Inositol; D002794:Choline