Maestri N E, Lord C, Glynn M, Bale A, Brusilow S W
Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Medicine (Baltimore). 1998 Nov;77(6):389-97.
Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of urea synthesis. Among females who carry a mutant OTC allele, there is a wide range of phenotypic variability, ranging from apparent normality to a severe onset and the resulting profound neurologic impairment observed in hemizygous males. This study was designed to define the phenotypic variability of OTC deficiency in ostensibly healthy carrier females and to compare them to noncarrier females from their own and other families. One hundred seventy-five women from 89 families participated in this study. Each completed a mailed questionnaire, allopurinol testing, and fasting plasma amino acid determinations. OTC carrier status was determined by pedigree analysis, allopurinol test results, and/or DNA mutation analysis. Overall, 79 women were identified as carriers of a mutant OTC allele (60 proband mothers, 19 relatives), and 96 women (32 proband mothers, 64 female relatives) were determined to be noncarriers. Comparison of biochemical phenotypes indicated that carriers and noncarriers do not differ in daily urinary creatinine excretion, but that carriers excrete significantly less urea nitrogen and total nitrogen, reflecting their significantly lower historically reported daily protein intake. Carriers had significantly higher levels of fasting plasma glutamine and alanine, and significantly lower levels of citrulline and arginine compared with noncarriers. Carriers and noncarriers reported similar demographic characteristics, anthropometric measurements, level of education, and medical and pregnancy histories. There was no indication of increased incidence of migraine headaches among carriers. Thus, we found no evidence that asymptomatic adult female OTC heterozygotes are at increased risk for previously unidentified health problems apart from an unknown risk for hyperammonemic encephalopathy as occurred in 3 of the carriers in this study. Because these episodes appear to be related to physiologic stress (fracture, parturition), it would seem medically prudent for carriers to be aware of this risk.
鸟氨酸转氨甲酰酶（OTC）缺乏症是一种X连锁的尿素合成障碍疾病。在携带突变OTC等位基因的女性中，存在广泛的表型变异，从看似正常到严重发病以及在半合子男性中观察到的严重神经功能损害。本研究旨在确定表面健康的携带者女性中OTC缺乏症的表型变异，并将她们与来自其自身及其他家庭的非携带者女性进行比较。来自89个家庭的175名女性参与了本研究。每个人都完成了一份邮寄问卷、别嘌呤醇检测和空腹血浆氨基酸测定。通过系谱分析、别嘌呤醇检测结果和/或DNA突变分析确定OTC携带者状态。总体而言，79名女性被确定为突变OTC等位基因的携带者（60名先证者母亲，19名亲属），96名女性（32名先证者母亲，64名女性亲属）被确定为非携带者。生化表型比较表明，携带者和非携带者在每日尿肌酐排泄方面没有差异，但携带者排泄的尿素氮和总氮明显较少，这反映出她们历史上报导的每日蛋白质摄入量明显较低。与非携带者相比，携带者的空腹血浆谷氨酰胺和丙氨酸水平显著较高，瓜氨酸和精氨酸水平显著较低。携带者和非携带者报告的人口统计学特征、人体测量指标、教育水平以及医疗和妊娠史相似。没有迹象表明携带者中偏头痛的发病率增加。因此，我们没有发现证据表明无症状成年女性OTC杂合子除了本研究中3名携带者发生的高氨血症性脑病的未知风险外，还有其他未被识别的健康问题的风险增加。由于这些发作似乎与生理应激（骨折、分娩）有关，从医学角度看，携带者了解这种风险似乎是谨慎的做法。
