新生儿尿素循环障碍5例临床分析

doi:10.12372/jcp.2023.22e1656

Abstract

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

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.

Figures/Tables 4

References 26

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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

Clinical analysis of urea cycle disorders in 5 neonates

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