Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile.
BACKGROUND
The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy.


METHODS
In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis.


RESULTS
The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity.


CONCLUSIONS
The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.
Harada
Eimei
E
Department of Pediatrics and Child Health, Kurume University School of Medicine, Asahi-machi, Kurume, Japan.
Nishiyori
Atsushi
A
Tokunaga
Yasuyuki
Y
Watanabe
Yoriko
Y
Kuriya
Norikazu
N
Kumashiro
Ryukichi
R
Kuno
Tateo
T
Kuromaru
Ryuichi
R
Hirose
Shinichi
S
Ichikawa
Kotaro
K
Yoshino
Makoto
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000596:Amino Acids / Q000097:blood*; D000641:Ammonia / Q000097:blood; D002648:Child; D005973:Glutamine / Q000097:blood; D006801:Humans; D008099:Liver / Q000201:enzymology; D008239:Lysine / Q000097:blood; D008297:Male; D008875:Middle Aged; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D011379:Prognosis; D012044:Regression Analysis
D000596:Amino Acids; D005973:Glutamine; D000641:Ammonia; D008239:Lysine