Harada Eimei, Nishiyori Atsushi, Tokunaga Yasuyuki, Watanabe Yoriko, Kuriya Norikazu, Kumashiro Ryukichi, Kuno Tateo, Kuromaru Ryuichi, Hirose Shinichi, Ichikawa Kotaro, Yoshino Makoto
Department of Pediatrics and Child Health, Kurume University School of Medicine, Asahi-machi, Kurume, Japan.
Pediatr Int. 2006 Apr;48(2):105-11. doi: 10.1111/j.1442-200X.2006.02181.x.
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.
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.
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.
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.
现已认识到鸟氨酸转氨甲酰酶（OTC）缺乏症男性患者在青春期或成年期发病的情况。本研究的目的是确定影响生存预后的因素，探索治疗策略的依据。
在10例患者中，9例携带OTC基因的R40H突变，另1例携带Y55D突变，首先使用非配对t检验比较幸存者和非幸存者之间的32项人口统计学和实验室数据。然后对有显著差异的因素进行多元回归分析。
显示出显著差异的因素有：发病年龄、血浆铵浓度、血液pH值以及血浆中六种氨基酸的浓度。多元回归分析随后显示铵、亮氨酸、赖氨酸、异亮氨酸、苯丙氨酸、谷氨酰胺和脯氨酸的浓度是显著的预后因素。10例患者的氨基酸谱显示谷氨酰胺、脯氨酸、赖氨酸、缬氨酸和蛋氨酸增加，丝氨酸、鸟氨酸和精氨酸减少。发病年龄与残余肝脏OTC活性水平呈负相关。
结果表明：（i）与其他肝脏疾病相比，血浆氨基酸谱具有独特性；（ii）上述六种氨基酸中每种氨基酸的血浆浓度是预后的重要预测指标；（iii）非幸存者中异亮氨酸和亮氨酸浓度较高表明抑制蛋白质分解代谢、预防谷氨酰胺诱导的脑水肿、纠正碱中毒以及补充鸟氨酸或精氨酸可能改善生存预后。
