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浙江大学学报(医学版)  2022, Vol. 51 Issue (3): 278-283    DOI: 10.3724/zdxbyxb-2022-0214
专题报道     
北京市新生儿短链酰基辅酶A脱氢酶缺乏症筛查、临床特征及基因突变分析
宫丽霏,杨楠,赵金琦,杨海河,唐玥,李璐璐,孔元原()
首都医科大学附属北京妇产医院 北京妇幼保健院新生儿疾病筛查科,北京 100026
Clinical characteristics and related gene mutations of infants with short-chain acyl-CoA dehydrogenase deficiency by neonatal screening in Beijing
GONG Lifei,YANG Nan,ZHAO Jinqi,YANG Haihe,TANG Yue,LI Lulu,KONG Yuanyuan()
Department of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
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摘要:

目的:探讨北京市新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)的发病率、临床特征及基因突变特点。方法:采用串联质谱法检测2014年8月至2022年3月北京市100?603名新生儿干血斑中酰基肉碱水平,采用气相色谱-质谱法检测尿有机酸,高通量测序检测基因突变。对SCADD确诊患儿进行临床、生化指标检查及基因突变特点分析,并随访患儿的生长发育和智能发育情况。结果:100 603名活产新生儿中初筛丁酰基肉碱(C4)浓度升高或伴C4/丙酰基肉碱(C3)比值升高196名,召回131名新生儿,确诊SCADD患儿5例,SCADD发病率为4.97/10万(1/20?121)。5例确诊患儿均无明显临床表现,血C4及C4/C3比值均增加,其中4例尿乙基丙二酸增加。5例确诊患儿中,ACADS基因检测到7种突变,均为已报道错义突变,其中1例患儿为纯合突变,其余均为复合杂合突变。5例患儿的随访年龄中位数为33(4~40)个月,随访期间均未出现临床症状,体格及智力发育正常。结论:北京市SCADD发病率为1/20?121,通过新生儿筛查确诊的SCADD患儿无明显临床症状,预后较好。

关键词: 短链酰基辅酶A脱氢酶缺乏症短链酰基辅酶A脱氢酶基因突变串联质谱法新生儿筛查随访研究    
Abstract:

Objective: To investigate the clinical characteristics of infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) and related gene mutations in Beijing. Methods: The acylcarnitine levels in the blood samples of 100?603 neonates in Beijing during August 2014 and March 2022 were measured by tandem mass spectrometry (MS/MS). The suspected SCADD neonates were rechecked by MS/MS, urine gas chromatography-mass spectrometry (GC/MS) and next-generation sequencing (NGS) for diagnosis. The clinical, biochemical and gene mutation characteristics of infants with SCADD were analyzed; the growth and intellectual development of these patients were observed regularly. Results: Among 100 603 live births, the elevated C4 concentration or elevated C4/C3 ratio were detected in the initial screening from 196 neonates, and 131 were recalled. Five cases of SCADD were diagnosed with an incidence rate of 4.97/100?000 (1/20?121). There was no significant abnormality in clinical manifestations, however, the blood butyrylcarnitine (C4) level and the ratio of C4 to propionylcarnitine (C3) were raised in all diagnosed cases. Urinary organic acids were analyzed in 4 cases, all of whom had increased ethyl malonate acid levels. Seven mutations were detected in the ACADS gene, all of which were known missense mutations. One patient had homozygous mutation, and the others showed compound heterozygous mutations. No clinical symptoms were observed, and the physical and intellectual development was normal in all patients at a median age of 33 (4-40) months during follow-up. Conclusions: The incidence rate of SCADD was 1/20?121 in Beijing. Neonates with early diagnosis and without clinical symptoms usually have good prognosis.

Key words: Short-chain acyl-CoA dehydrogenase deficiency    Short-chain acyl-CoA dehydrogenase    Gene mutation    Tandem mass spectrometry    Neonatal screening    Follow-up studies
收稿日期: 2022-04-30 出版日期: 2022-09-21
CLC:  R596  
通讯作者: 孔元原     E-mail: kongyuanyuan1971@mail.ccmu.edu.cn
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引用本文:

宫丽霏,杨楠,赵金琦,杨海河,唐玥,李璐璐,孔元原. 北京市新生儿短链酰基辅酶A脱氢酶缺乏症筛查、临床特征及基因突变分析[J]. 浙江大学学报(医学版), 2022, 51(3): 278-283.

GONG Lifei,YANG Nan,ZHAO Jinqi,YANG Haihe,TANG Yue,LI Lulu,KONG Yuanyuan. Clinical characteristics and related gene mutations of infants with short-chain acyl-CoA dehydrogenase deficiency by neonatal screening in Beijing. J Zhejiang Univ (Med Sci), 2022, 51(3): 278-283.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0214        https://www.zjujournals.com/med/CN/Y2022/V51/I3/278

例序

初筛

复查

ACADS突变及致病风险

随访

转归c

出生后时间(d)

C4a

C4/C3比值

出生后时间(d)

C4a

C4/C3比值

乙基丙二酸b

月龄

C4a

C4/C3比值

乙基丙二酸b

1

7

1.14

1.46

23

2.06

1.89

123.21

c.1031A>G(p.Glu344Gly)(父):Pc.1067C>T(p.Ala356Val)(母):P

40

正常

2

3

0.52

0.34

32

1.00

1.03

79.07

c.391G>A(p.Gly131Ser)(父):VUS

c.989G>A(p.Arg330His) (母):LP

38

0.75~1.68

0.58~2.10

93.73

正常

3

4

1.86

1.24

16

1.56

1.66

c.1031A>G(p.Glu344Gly) (父):P

c.1031A>G(p.Glu344Gly) (母):P

33

1.62~3.09

1.69~5.42

52.90~115.45

正常

4

3

0.97

1.01

17

0.57

0.54

16.42

c.625G>A(p.G209S)(父):VUS

c.1195C>T(p.R399W)(母):LP

19

0.51~0.68

0.32~0.52

13.64~16.22

正常

5

3

0.71

0.38

14

0.57

0.52

13.40

c.625G>A(p.G209S)(父):VUS

c.625G>A(p.G209S)(母):VUS

c.136C>T(p.R46W)(母):P

4

0.68

0.44

正常

表 1  五例短链酰基辅酶A脱氢酶缺乏症患儿的诊断及随访情况
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