ORNITHINE TRANSCARBAMYLASE DEFICIENCY IN WOMEN

女性鸟氨酸转氨酰酶缺乏症

• 批准号: 3330534
• 负责人: SAUL W BRUSILOW
• 金额: $ 17.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3330534
• 关键词: blood chemistry; cytogenetics; dietary control; disease /disorder proneness /risk; disease carrier state; enzyme deficiency; family genetics; female; gene expression; gene mutation; genetic disorder diagnosis; genetic polymorphism; high performance liquid chromatography; human genetic material tag; human morbidity; human mortality; human subject; liver function; medical complication; nitrogen balance; nutrition related tag; ornithine carbamoyl phosphate deficiency; ornithine carbamoyltransferase; phenotype; questionnaires; sex linked trait; statistics /biometry; urinalysis

OTC is an X-linked disorder of nitrogen homeostasis which has phenotypic variability in males and females. Variability in males is principally a function of mutational variability whereas variability in females is principally a function of random X-chromosome reactivation. The goal of this project is to investigate the phenotypic variability in adult women who have a mutation at the ornithine transcarbamylase (OTC) locus. Recent evidence suggests that many of these women have detectable metabolic abnormalities and may be at risk for life-threatening hyperammonemia. At-risk adult females for this study will be ascertained through 270 pedigrees of OTC deficient probands already identified by the Johns Hopkins Center for Urea Cycle Disorders; additional at-risk females will be recruited as new OTC deficient patients are referred. In pedigrees ascertained through a proband with OTC deficiency, untested at-risk adult females will be asked to take an allopurinol test to determine their carrier status. This test requires the careful collection of four timed urine specimens during a 24 hour period. Urine and plasma samples will also be obtained to measure biochemical variables associated with OTC deficiency. Self-administered questionnaires covering family history, demographic, education, dietary and medical information will be distributed to these women. Based on the results of the allopurinol tests, carrier and non-carrier females will be identified and compared to determine if carriers experience excess morbidity or premature mortality, decreased educational achievement or voluntary restriction of dietary protein. In addition, the relationship between abnormal biochemical measurements and unfavorable clinical outcomes in carriers will be examined. Identification of specific abnormalities in adult carrier females will allow better and more appropriate treatment for carriers of this mutant allele.

OTC是一种具有表型的氮稳态疾病 男性和女性的变异性。 男性的可变性主要是 突变可变性的功能，而女性的变异性是 主要是随机X染色体重新激活的函数。 该项目的目的是调查表型变异性 在鸟氨酸经钙化酶（OTC）处有突变的成年女性 轨迹。 最近的证据表明，其中许多妇女有可检测到的 代谢异常，可能有威胁生命的风险 高症血症。 这项研究的高危成年女性将通过270确定 Johns已经确定的OTC缺陷概率的血统 霍普金斯尿素周期疾病中心；额外的高危女性将 被推荐为新的OTC缺乏患者，被招募。 在谱系中 通过OTC缺乏症来确定未经测试的高危成人 女性将被要求参加别嘌醇的测试以确定自己的 载体状态。 该测试需要仔细收集四个计时 尿液标本在24小时内。 尿液和血浆样品将 还可以获得与OTC相关的生化变量 不足。 涵盖家族史的自我管理问卷， 人口，教育，饮食和医学信息将是 分发给这些妇女。 基于别嘌呤醇测试的结果，载体和非载体 将确定女性并进行比较以确定载体是否 经历过多的发病率或过早死亡，教育程度下降 饮食蛋白的成就或自愿限制。 此外， 异常生化测量与 将检查载体中不利的临床结果。 识别成年载体女性特定异常的识别 为该突变体的载体提供更好，更合适的治疗 等位基因。