新生儿尿素循环障碍5例临床分析

doi:10.12372/jcp.2023.22e1656

摘要/Abstract

摘要：

目的总结新生儿尿素循环障碍（UCDs）的临床特征、诊治过程、转归及预后，以提高对该病的认识。方法回顾性分析2017年7月至2022年7月收治的经基因测序证实为阳性变异的5例新生儿UCDs的临床特点、治疗及预后等资料。结果 5例新生儿中男4例、女1例，胎龄（39.0±1.2）周，出生体重（3 642.0±511.6）g，中位发病日龄2（1~5）d，初始血氨水平（1 386.8±398.4）μmol/L。起病特征分别为纳差3例、低体温2例、气促2例、呕吐1例，均有肌张力减退、意识障碍及惊厥。原发病为鸟氨酸氨甲酰转移酶缺乏症(OTCD)3例，氨甲酰磷酸合成酶1缺乏症（CPS1D）2例。OTCD患儿瓜氨酸降低，尿乳清酸增高，存在3种基因致病变异，其中c.177delA和c.387-1G>T为新发变异。CPS1D患儿瓜氨酸降低，尿乳清酸浓度正常或降低，基因测序存在4个变异位点，其中c.548T>C和c.3G>C为新发变异。5例UCDs新生儿均在饮食控制及药物治疗的基础上叠加透析疗法以快速清除血氨，其中3例患儿血氨水平降至（164.0±47.1）μmol/L，但因神经系统不良预后，最终4例放弃治疗后死亡，1例存活。存活患儿在1岁时接受了肝移植手术，随访至2022年12月存在语言及运动发育落后。结论新生儿UCDs病死率高且预后差，临床起病特征常缺乏特异性，尽早的血氨检测是发现该病的关键，基因分析可明确诊断。尽早给予有效干预可挽救患儿生命及改善其神经系统预后。

关键词: 高氨血症, 尿素循环障碍, 临床分析, 新生儿

Abstract:

Objective To summarize the clinical features, diagnosis and treatment, regression and prognosis of 5 neonatal urea cycle disorders (UCDs) in order to improve the understanding of the disease. Methods The clinical characteristics, treatment and prognosis of 5 neonatal UCDs confirmed by gene sequencing admitted from July 2017 to July 2022 were retrospectively analyzed. Results The gestational age of the five neonates (4 boys and 1 girl) was (39.0±1.2) weeks, the birth weight was (3642.0±511.6) g, the age of onset was 2(1-5) days, and the initial blood ammonia level was (1386.8±398.4) μmol/L. The onset characteristics of the children were poor appetite (3 cases), hypothermia (2 cases), shortness of breath (2 cases) and vomiting (1 case). All the children had hypotonia, disturbance of consciousness and convulsion. The primary disease was ornithine transcarbamylase deficiency (OTCD) in 3 cases and carbamoyl phosphate synthase 1 deficiency (CPS1D) in 2 cases. Decreased citrulline and increased urinary orotate was found in children with OTCD, and there were three gene pathogenic variants, among which c.177delA and c.387-1G>T were new variants. In CPS1D children, citrulline was decreased, urinary orotate concentration was normal or decreased, and four variation loci were found by gene sequencing, among which c.548T>C and c.3G>C were new variants. All 5 neonates with UCDs were treated with diet control and medication followed by dialysis for rapid clearance of ammonia, and the blood ammonia level in 3 of them decreased to (164.0±47.1) μmol/L. However, due to the poor prognosis of the nervous system, 4 patients died and 1 patient survived. The surviving neonate underwent liver transplantation at the age of 1 year and was followed up until December 2022. The child had delayed language and motor development. Conclusions UCDs in newborns have a high mortality rate and a poor prognosis, and the clinical features are often unspecific. Early blood ammonia detection is the key to detect the disease, and genetic analysis can confirm the diagnosis. Early and effective intervention can save the children’s life and improve their neurological prognosis.

Key words: hyperammonemia, urea cycle disorder, clinical analysis, neonate

楚晓云, 孙祎璠, 颜崇兵, 洪文超, 龚小慧, 蔡成. 新生儿尿素循环障碍5例临床分析[J]. 临床儿科杂志, 2023, 41(4): 266-271.

CHU Xiaoyun, SUN Yifan, YAN Chongbing, HONG Wenchao, GONG Xiaohui, CAI Cheng. Clinical analysis of urea cycle disorders in 5 neonates[J]. Journal of Clinical Pediatrics, 2023, 41(4): 266-271.

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病例	性别	胎龄/周	出生体重/g	入院日期	发病日龄/d	起病特征	危重症评分	预后
1	男	38⁺¹	3 750	2018.12	8	呕吐、嗜睡	88	存活
2	男	39⁺¹	3 460	2017.12	1	气促、纳差	80	死亡
3	男	38	2 850	2022.07	1	纳差	80	死亡
4	男	41	4 080	2019.02	2	低体温、纳差	86	死亡
5	女	38⁺⁵	4 070	2021.02	2	气促、低体温	80	死亡

病例	初始血氨/ μmol·L^-1	乳酸/ mmol·L^-1	谷氨酰胺/ μmol·L^-1	瓜氨酸/ μmol·L^-1	精氨酸/ μmol·L^-1	尿嘧啶/mmol·molCr^-1	尿乳清酸/ mmol·molCr^-1	治疗后血氨/ μmol·L^-1
1	700	3.0	1 577.3	2.7	6.1	32.0	352.1	218
2	1 574	13.7	2 776.5	4.9	26.7	-	110.8	131
3	1 700	14	3 841.2	4.6	9.7	-	106.4	1 700
4	1 560	3.9	1 204.4	1.6	5.3	-	0.4	1 560
5	1 400	6.8	1 281.1	4.3	6.5	-	1.0	143
参考值	16~60	0.5~2.2	5~1 150	6~50	0.8~60	0~19.7	0~2.5	16~60

病例	突变基因	核苷酸变化	氨基酸变化	遗传方式	原发病	变异来源
1	OTC	c.803T>C	p. Met268Thr	XL	OTCD	母亲
2	OTC	c.177delA	p.S60QfsTer4	XL	OTCD	母亲
3	OTC	c.387-1G>T	-	XL	OTCD	母亲
4	CPS1	c.3784C>T c.3734T>A	p.Arg1262 p.Leu1245His	AR	CPS1D	母亲父亲
5	CPS1	c.548T>C c.3G>C	-	AR	CPS1D	父母未检测

病例	糖速/ mg·kg^－1·min^－1	脂肪/ g·kg^－1·d^－1	热卡/ kcal·kg^－1·d^－1	静脉营养时间/d	腹膜透析循环次数/次·d^－1	腹膜透析时间/d	CRRT模式	CRRT时间/d	住院时间/d
1	8	1~2	95~100	6	8~12	3	-	-	6.5
2	8	0.5	80~100	8	-	-	CVVHDF	4.5	7.5
3	8	0.5	80	0.5	24	0.5	-	-	0.5
4	8	1	90	2.5	-	-	CVVHDF	1	2.5
5	8.5~10	0.5~1.5	100~110	8	-	-	CVVHDF	4.5	8.5