OTC基因新变异致鸟氨酸氨甲酰基转移酶缺陷病1例报告

Late-onset Ornithine Transcarbamylase Deficiency Caused by a Novel Variant of the OTC Gene:A Case Report

目的报告1例鸟氨酸氨甲酰基转移酶缺陷病(ornithine transcarbamylase deficiency,OTCD)患儿的临床及分子遗传学特点,为本病诊疗提供参考。方法回顾性分析一例OTCD患儿临床和实验室资料。结果患儿女性,1岁6月,因“反复呕吐伴烦躁不安4月余”就诊。查体发现双下肢张力减退,双侧膝关节反射亢进,双侧踝阵挛阳性。血生化谷丙转氨酶、谷草转氨酶及血氨升高,尿液有机酸分析显示尿嘧啶、乳清酸和4-羟基苯乳酸水平升高。遗传学分析在患儿OTC基因检出c.612614del(p.Ile204del)新生变异,结合ACMG标准判断该变异具有致病性。经限制蛋白质摄入、精氨酸、瓜氨酸和苯甲酸钠等治疗后患儿病情控制仍不理想,于2岁时进行肝移植治疗,移植后患儿肝功能和血氨恢复正常。结论本文通过临床和遗传学研究,发现1个OTC新变异c.612614del,确诊了一例OTCD患儿,为本病确诊和遗传咨询提供了遗传学标记物,同时为临床和实验室特征的科学认识积累了资料。

Objective This study aimed to report the clinical and molecular genetic characteristics of a patient with late-onset ornithine transcarbamylase deficiency(OTCD),so as to help reference for the diagnosis and treatment of the disease.Methods The clinical and laboratory data of a pediatric patient with OTCD were retrospectively analyzed.Results:The patient was a female aged 1 year and 6 months with the complaint of"recurrent vomiting and restlessness over 4 months".Physical examination revealed bilateral hypotonia of the lower limbs,hyperreflexia of the knees,and clonus of the ankles.Laboratory analysis revealed elevated levels of serum ammonia as well as transaminases.On urinary organic acids analysis,a large quantity of uracil,orotate and 4-hydroxyphenyllactate was detected.The patient was heterozygous for the de novo variant c.612_614del(p.Ile204del)in the OTC gene,which was evaluated“pathogenic”according to the ACMG standard and guideline.OTCD was diagnosed,and uptake restriction of proteins and oral administration of arginine,arginine citrulline and sodium benzoate were given.However,the response of the patient was not promising,and hence liver transplantation was underwent at her age of 2 years.As a result,the liver function and blood ammonia returned to normal.Conclusion Through clinical and genetic research,this study identified a novel OTC variant c.612_614del in a patient with OTCD.The findings provided genetic markers for the diagnosis of OTCD and genetic counseling in the affected family,and accumulated data for the scientific understanding of the clinical and laboratory characteristics of this disease.