<strong>31</strong>例新生儿筛查阴性的先天性甲状腺功能减退症患儿临床特点及转归

doi:10.3724/zdxbyxb-2022-0213

浙江大学学报（医学版）

2022, Vol. 51

Issue (3): 314-320 DOI: 10.3724/zdxbyxb-2022-0213

专题报道

31例新生儿筛查阴性的先天性甲状腺功能减退症患儿临床特点及转归

谢婷¹,谭敏沂¹,蒋翔¹,冯瑜妤¹,陈倩瑜¹,梅慧芬²,蔡雁英¹,邹红梅^3,*(

),黄永兰^1,*(

)

1.广州市妇女儿童医疗中心广州市新生儿筛查中心广东省儿童健康与疾病临床医学研究中心，广东广州 510623
2.广州市妇女儿童医疗中心遗传与内分泌科广东省儿童健康与疾病临床医学研究中心，广东广州 510623
3.广州市妇女儿童医疗中心新生儿科广东省儿童健康与疾病临床医学研究中心，广东广州 510623

Clinical features and outcomes of 31 children with congenital hypothyroidism missed by neonatal screening

XIE Ting¹,TAN Minyi¹,JIANG Xiang¹,FENG Yuyu¹,CHEN Qianyu¹,MEI Huifen²,CAI Yanying¹,ZOU Hongmei^3,*(

),HUANG Yonglan^1,*(

)

1. Guangzhou Women and Children’s Medical Center, Guangzhou Newborn Screening Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China;
2. Department of Pediatric Endocrinology and Genetic Metabolism, Guangzhou Women and Children’s Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China;
3. Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China

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摘要：

目的：探讨新生儿筛查阴性的先天性甲状腺功能减退症（CH）患儿的临床特点及转归。方法：回顾性分析2015年2月至2022年2月广州市妇女儿童医疗中心确诊的31例筛查阴性CH患儿的临床、实验室资料，其中17例进行了全外显子组高通量测序基因分析。结果：31例CH患儿中，早产儿19例（61.3%），足月儿12例（38.7%），胎龄36（26~40）周，出生体重2.35（0.75~3.70）kg，诊断年龄20?d（7?d~4岁），初筛干血斑促甲状腺素4.18（0.34~8.97）mU/L。同性别双胎儿9例（29.0%），有甲状腺功能减退家族史4例（12.9%）。首发症状为体重增长缓慢11例（35.5%），黄疸消退延迟7例（22.6%），矮小症、腹胀伴脐疝、胎儿水肿、甲状腺肿各1例（3.2%）。17例患儿全外显子组测序结果显示，10例检出DUOX2基因突变（携带双位点突变6例，携带单位点突变4例），其中3例伴甲状腺功能减退家族史。22例进行了诊断再评估，其中17例（77.3%）为暂时性CH，5例（22.7%）为永久性CH。10例DUOX2基因突变患儿中，6例为暂时性CH，1例为永久性CH，3例（均为3岁以下）仍在治疗中。结论：CH筛查假阴性多见于早产、低出生体重、同性别双胎、有甲状腺功能减退家族史患儿，DUOX2基因突变是常见的分子生物学发病基础，多数患儿为暂时性CH。对不明原因生长缓慢、黄疸消退延迟患儿应及时进行甲状腺功能评估，以便早期诊断。

关键词： 先天性甲状腺功能减退症; 新生儿筛查; 假阴性; DUOX2基因; 预后

Abstract:

Objective: To investigate the clinical features and outcomes of children with congenital hypothyroidism (CH) missed by neonatal screening. Methods: The clinical and laboratory date of 31 children with CH missed by neonatal screening from February 2015 to February 2022 in Guangzhou Women and Children’s Medical Center were retrospectively analyzed. Whole-exome high-throughput sequencing analysis was performed in 17 patients. Results: Among the 31 patients, 19 cases (61.3%) were preterm, 12 cases (38.7%) were term neonates. The median value of gestation age was 36 (26-40) weeks, birth weight was 2.35 (0.75-3.70)?kg, diagnosed age was 20?d (7?d-4?years), dry blood spot thyrotropin was 4.18 (0.34-8.97)?mU/L. Nine cases (29.0%) were same-sex twins and 4 cases (12.9%) had a family history of hypothyroidism. The initial clinical symptoms were growth retardation in 11 cases (35.5%), prolonged jaundice in 7 cases (22.6%), short stature, abdominal distension, fetal edema and goiter in 1 case (3.2%), respectively. Genetic analysis of the 17 children showed that DUOX2 gene mutations were detected in 10 cases (6 cases with biallelic mutations and 4 cases with monoallelic mutations), of whom 3 had a family history of hypothyroidism. A total of 22 patients were reevaluated at the age of 2-3?years, of whom 17 cases (77.3%) were transient CH and 5 cases (22.7%) were permanent CH. Among the 10 cases with DUOX2 gene mutations, 6 cases were transient CH, 1 case was permanent CH, and 3 cases (< 3 years old) were still under treatment with L-thyroxine.Conclusions: False negative results on neonatal screening for CH often occurs in preterm birth, low birth weight, same-sex twins, family history of hypothyroidism, and DUOX2 defects are the common molecular pathogenesis, most of whom are transient CH. Thyroid function should be evaluated in time for children with unexplained slow growth and delayed jaundice regression.

Key words: Congenital hypothyroidism Neonatal screening False negative DUOX2 gene Prognosis

收稿日期: 2022-04-29 出版日期: 2022-09-21

CLC:

R72

基金资助: 广州市科技计划项目（201510010010）

通讯作者: 邹红梅,黄永兰 E-mail: xxhuang321@163.com

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引用本文:

谢婷,谭敏沂,蒋翔,冯瑜妤,陈倩瑜,梅慧芬,蔡雁英,邹红梅,黄永兰. 31例新生儿筛查阴性的先天性甲状腺功能减退症患儿临床特点及转归[J]. 浙江大学学报（医学版）, 2022, 51(3): 314-320.

XIE Ting,TAN Minyi,JIANG Xiang,FENG Yuyu,CHEN Qianyu,MEI Huifen,CAI Yanying,ZOU Hongmei,HUANG Yonglan. Clinical features and outcomes of 31 children with congenital hypothyroidism missed by neonatal screening. J Zhejiang Univ (Med Sci), 2022, 51(3): 314-320.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0213 或 https://www.zjujournals.com/med/CN/Y2022/V51/I3/314

例序	性别	胎龄（周）	出生体重（kg）	bsTSH （mU/L）	诊断年龄	sTSH （mU/L）	FT₄ （pmol/L）	TG （μg/L）	甲状腺超声检查	药物维持剂量（μg/d）	转归	DUOX2基因
1	男	28	0.75	2.70	27?d	>150.0	5.5	—	正常	12.5	6月龄夭折	—
2	男	28	0.65	1.60	29?d	15.1	14.8	—	正常	12.5	暂时性CH	—
3	男	34	2.35	2.90	10?d	75.0	7.5	59.0	增大	12.5	暂时性CH	p.Ser199TrpfsX122/p.Arg683Leu
4	男	34	2.40	1.67	13?d	85.0	6.8	73.2	增大	12.5	暂时性CH	p.Ser199TrpfsX122/p.Arg683Leu
5	男	28	1.31	0.34	12?d	89.4	5.4	101.3	—	10.0	暂时性CH	—
6	女	34	1.35	5.90	20?d	28.0	8.7	—	增大	12.5	暂时性CH	—
7	女	36	2.15	5.27	43?d	10.1	14.9	82.0	增大	12.5	永久性CH	p.Ile1130Phe^#
8	女	36	2.25	6.82	18?d	51.6	11.2	369.3	增大	25.0	暂时性CH	—
9	女	38	3.10	4.31	19?d	36.4	14.9	118.0	增大	12.5	暂时性CH	—
10	女	26	0.80	2.69	31?d	61.8	6.9	—	正常	12.5	2月龄夭折	—
11	男	26	1.01	2.65	21?d	18.8	13.3	—	正常	6.3	暂时性CH	—
12	女	27	1.18	3.12	15?d	127.3	4.3	—	—	12.5	治疗中	—
13	男	30	1.40	2.91	24?d	31.3	12.4	81.7	正常	12.5	暂时性CH	p.Tyr1450His/ p.Gly702del
14	女	32	2.12	4.05	14?d	>150.0	5.7	—	—	25.0	治疗中	—
15	女	32	1.85	3.29	33?d	90.9	18.9	135.0	增大	10.0	暂时性CH	未见异常
16	男	34	2.58	5.05	7?d	16.5	14.5	—	正常	25.0	暂时性CH	未见异常
17	男	34	3.38	3.65	18?d	>150.0	6.3	—	—	37.5	50?d夭折	—
18	男	35	2.48	3.46	27?d	56.5	10.6	66.1	正常	12.5	暂时性CH	未见异常
19	女	36	2.30	7.50	60?d	34.2	11.9	107.0	正常	25.0	永久性CH	—
20^*	男	36	2.70	6.83	15?d	>150.0	8.5	67.0	增大	17.0	暂时性CH	p.Lys530X/p.Ala649Glu
21	女	38	2.07	7.05	9?d	37.0	15.9	62.7	增大	25.0	暂时性CH	未见异常
22^*	女	38	2.24	8.97	9?d	33.6	14.9	24.5	正常	12.5	治疗中	p.Arg434X
23	男	38	3.25	8.72	15?d	86.0	7.0	9.3	正常	12.5	治疗中	未见异常
24	男	39	3.20	4.07	22?d	23.0	13.1	67.7	正常	12.5	治疗中	p.Lys530X/p.Arg885Leu
25	男	39	3.70	5.54	27?d	51.8	10.3	—	增大	12.5	治疗中	p.Ser1349Cys
26	男	39	2.48	5.25	15?d	41.8	13.7	639.0	正常	37.5	永久性CH	未见异常
27	女	39	2.90	4.18	2岁半	37.0	8.8	—	增大	37.5	永久性CH	—
28	男	40	3.29	8.27	13?d	31.6	14.4	34.2	正常	12.5	暂时性CH	—
29	女	40	2.85	4.02	21?d	89.3	9.4	999.4	正常	17.0	暂时性CH	p.Glu879Lys
30^*	女	40	3.18	8.79	60?d	9.7	11.1	—	增大	25.0	暂时性CH	p.Arg683Leu/p.Lys530X
31^*	女	39	3.20	8.86	4岁	15.4	17.3	17.0	正常	37.5	永久性CH	未见异常

表 1 31例新生儿筛查阴性的CH患儿临床特征及外显子测序结果

表 2 有无携带突变的先天性甲状腺功能减退症患儿生化指标检测结果比较

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