Wu Tongfei, Li Xiyuan, Ding Yuan, Liu Yupeng, Song Jinqing, Wang Qiao, Li Mengqiu, Qin Yaping, Yang Yanling
Youanmen Clinical Laboratory Center of Capital Medical University, Beijing 100069, China.
Email:
Zhonghua Er Ke Za Zhi. 2015 Jun;53(6):425-30.
Argininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia.
Three boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis.
Seven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn.
Argininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.
精氨酸血症是一种罕见的尿素循环缺陷疾病。该疾病的临床表现与脑瘫相似，因此诊断通常会延迟很久。本研究旨在调查7例中国精氨酸血症患者的表型和基因型。
通过血液氨基酸分析和ARG1基因研究，3名男孩和4名患有痉挛性四肢瘫的女孩被诊断为精氨酸血症。患者接受了蛋白质限制饮食、瓜氨酸、苯甲酸钠及其他治疗干预。5号和6号患者的母亲接受了遗传咨询，并通过羊膜穿刺术进行了产前诊断。
7例患者在1个月至4岁时出现进行性痉挛性四肢瘫和身体发育不良。精氨酸血症在1岁10个月至12岁时被发现。5例患者有智力障碍。3例有癫痫发作。他们的血液精氨酸升高（86.66至349.83µmol/L，正常对照为5至25µmol/L）。6例患者发现肝功能障碍。5例患者血氨水平升高。4例患者通过头颅磁共振成像观察到脑萎缩。从7例患者中鉴定出ARG1基因的9个突变。只有两个突变，即外显子7中的c.703G>A和外显子1中的c.32T>C已被报道。c.34G>T、c.53G>A、c.67delG、c.232dupG、c.374C>T、c.539G>C和c.646 - 649delCTCA是ARG1基因的新突变。在5号患者母亲的羊膜细胞中发现了纯合突变c.703G>A，表明胎儿受精氨酸血症影响。实施了人工流产。在6号患者母亲的羊膜细胞中未发现来自6号患者的c.53G>A，表明胎儿未受肝细胞精氨酸酶缺乏影响。脐带血的产后突变分析和新生儿正常血液精氨酸证实了该结果。
精氨酸血症是小儿痉挛性麻痹少数可治疗的病因之一。在本研究中，通过血液氨基酸分析检测到7例中国痉挛性四肢瘫患者，并通过分子分析得以证实。鉴定出ARG1基因的7个新突变。通过羊膜细胞ARG1基因分析对一个家庭的胎儿进行了产前诊断。
