ACE基因突变致遗传性肾小管发育不良1例并文献复习  

One case of autosomal recessive renal tubule dysgenesis caused by ACE gene mutation and literature review

作　　者：朱叶芳[1] 汤磊 王雪燕[1] 王彬[1] 刘明博[1] 宋思捷 钟晓云[1] ZHU Ye-fang;TANG Lei;WANG Xue-yan;WANG Bin;LIU Ming-bo;SONG Si-jie;ZHONG Xiao-yun(Chongqing Health Center for Women and Children,Chongqing 400021,China;Chongqing Banan District People's Hospital,Chongqing 401320,China)

机构地区：[1]重庆市妇幼保健院,重庆400021 [2]重庆巴南区人民医院,重庆401320

出　　处：《中国循证儿科杂志》2018年第5期373-379,共7页Chinese Journal of Evidence Based Pediatrics

摘　　要：目的提高对遗传性RTD的认识和早期诊断水平。方法报告1例确诊的遗传性RTD患儿的一般情况、肾脏病理、实验室检查和基因测序结果,系统检索文献并复习已报道的类似病例,总结遗传性RTD的遗传和临床特征。结果患儿女,因"早产后15 min,气促、发绀5 min"入重庆市妇幼保健院,胎龄28+2周,出生体重1 090 g,羊水0 mL,生后Apgar评分1和5 min分别为8和9分。母孕期正规产检,孕23^(+5)及26^(+1)周因"羊水少"行2次羊膜腔穿刺及0.9%生理盐水灌注术。母不良孕产史3次,均因"羊水少",或早产生后1 d夭折,或孕5月引产。患儿生后反应欠佳,轻度吸气性三凹征,心音有力、律齐,腹软,肝脾肋下未扪及,原始反射均减弱。予呼吸机辅助通气,予2次肺表面活性物质替代治疗,扩容和多巴胺应用下平均血压22～28 mmHg。应用呋塞米后尿量0.14～0.31 ml·kg^(-1)·h^(-1),患儿日龄44 h时家属放弃抢救治疗后死亡,尸体泌尿系组织病理诊断:肾小管大小不一,近端小管缺乏,部分远端小管及集合管发育不良。患儿为ACE基因复合杂合突变:c.538C>T来源于母亲,c.3073_3074delTC来源于父亲。共检索到11篇文献,报道了36个家系,加上本文共37个家系的64例ACE基因突变胎儿和婴儿,共发现40个ACE基因突变位点。9个家系为近亲结婚。每个家系均有1～4例母孕期羊水少的受累胎儿,羊水少开始于孕中期,早至18周;终止妊娠10例,死胎7例,出生后死亡39例(<3 d死亡33例,～28 d死亡6例;早产儿37例,足月儿2例),存活>1年8例(慢性肾疾病6例,肾移植1例,正常肾功能1例)。新生儿主要以呼吸困难、低血压、无尿为主要表现,部分病例伴有颅骨发育不良、小结肠(结肠直径0.5～0.6 cm)。结论对于遗传性RTD,完善基因检测对提高产前诊断及RTD早期诊断有重要意义。Objective To improve the early recognition and diagnosis of the neonates with autosomal recessive renal tubular dysgenesis(RTD).Methods A preterm infant with RTD was reported and the clinical data were collected.Clinical features and gene sequencing of similar cases from published literatures were reviewed and systematically summarized.Results The gestational age of the infant was 28+2 weeks and the birth weight was 1 090 g.No amniotic fluid was found and the Apgar scores were 8 at 1 min and 9 at 5 min.The antenatal care was performed regularly.In order to decrease the risk of oligohydramnios,the amniocentesis and amnioinfusion(with 0.9%normal saline)were performed at 23+5 weeks(290 mL)and 26+1 weeks(330 mL)during pregnancy.The previous three pregnancies were all complicated by oligohydramnios.The first baby died on the first day after birth,then the second and the third pregnancy were terminated at 22-23 weeks of gestational age.The baby showed poor response and respiratory distress,so high frequency oscillation ventilation was performed and pulmonary surfactant was administrated.Hypotension occured soon after birth and fluid therapy and dopamine were used,but hypotension was not controlled(mean arterial pressure 22-28 mmHg).Diuretics was used and urine output was only 0.14-0.31 mL·kg-1·h-1.The treatment was terminated requested by the parents,and the infant died at 44 h 45 min after birth.Renal histology revealed the absence of recognizable proximal tubules and dysgenesis of some distal renal tubules and collecting tubules,but with normal glomeruli.Two novel heterozygous mutations were identified in ACE gene(NM_000789)in this patient.Exon 4 was carrying a heterozygous nucleotide substitution c.538C>T predicting a premature stop codon(p.Arg180*),which was inherited from her mother,and in addition a paternally inherited heterozygous frameshift mutation c.3073_3074delTC(p.Ser1027Tyrfs*14)was found in exon 20.We found 11 articles in Chinese and PubMed database,which reported 36 families diagnosed as RTD with ACE

关 键 词：肾小管发育不良 羊水少 新生儿 低血压 ACE基因 

分 类 号：R726.9[医药卫生—儿科]