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浙江大学学报（医学版）
浙江大学学报（医学版）  2022, Vol. 51 Issue (3): 284-289    DOI: 10.3724/zdxbyxb-2022-0114
专题报道     
山东省淄博市241 297名新生儿中链酰基辅酶A脱氢酶缺乏症筛查及随访结果分析
董丽萍,季婵婵,许佳,崔艳国()
淄博市妇幼保健院新生儿疾病筛查中心，山东 淄博 255000
Screening and follow-up results of neonate medium-chain acyl-CoA dehydrogenase deficiency in Zibo, Shandong province
DONG Liping,JI Chanchan,XU Jia,CUI Yanguo()
Neonatal Screening Center, Zibo Maternal and Child Health Hospital, Zibo 255000, Shandong Province, China
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摘要：

目的：分析山东省淄博市中链酰基辅酶A脱氢酶缺乏症（MCADD）的发病率、表型、基因型及临床预后。方法：选择山东省淄博市2013年11月至2022年1月出生的241 297名新生儿作为研究对象。采用非衍生化串联质谱法检测血游离肉碱及酰基肉碱谱进行新生儿筛查，召回初筛及复筛辛酰基肉碱（C8）不低于0.25?μmol/L或合并C8/癸酰基肉碱（C10）不低于1.5的患儿，采用高通量测序进行基因检测并诊断。结果：241 297名新生儿中，检出MCADD患儿6例，男性2例，女性4例，发病率约为1/40 216。患儿均检测到ACADM基因2个突变位点，共检出12个突变8种突变类型，热点突变为c.449_452del（p.T150Rfs*4）和c.387+1delG，检出 1个新发突变为11号外显子c.1076C>T（p.A359V），未发现表型与基因型的相关性。6例MCADD患儿中，1例出生后第4天死亡；5例随访2~60个月，均未特殊饮食治疗，生长发育、智力发育正常，常规生化指标未见异常。结论：淄博市MCADD发病率较国内其他地区高，ACADM基因热点突变为c.449_452del（p.T150Rfs*4）和c.387+1delG，发现1个新发突变c.1076C>T（p.A359V），未发现表型与基因型的相关性。早期诊断、正确治疗是减少不良预后的有效措施。
关键词： 中链酰基辅酶A脱氢酶缺乏症;  ACADM基因;  新生儿筛查;  随访研究;  预后    
Abstract:

Objective: To analyze the incidence, phenotype, genotype and prognosis of neonatal medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in Zibo city of Shandong province. Methods: A total of 241 297 neonates were screened for MCADD in Zibo city of Shandong province from November 2013 to January 2022. Non-derivatized tandem mass spectrometry was used to detect blood free carnitine and acylcarnitine profiles in neonatal screening. Neonates with octanoylcarnitine (C8)≥0.25?μmol/L, or combined with C8/decanoylcarnitine (C10)≥1.5 were recalled, and second-generation high-throughput sequencing was performed for genetic diagnosis. Results: Among 241?297 neonates, 6 cases of MCADD were screened, including 2 boys and 4 girls, with an incidence of 1/40 216. Two mutation sites of ACADM gene were identified in all MCADD infants, and 12 mutation with 8 types were detected in total. The hot spot mutations were c.449_452del (p.T150Rfs*4) and c.387+1delG， and exon 11 c.1076C>T (p.A359V) was a newly detected mutation. No phenotype-genotype correlation was found. One case died on day 4 after birth; 5 cases were followed up for 2 to 60?months, none of them received special diet treatment. The growth and intellectual development of the surviving cases were normal, and no abnormality was found in routine biochemical indicators.Conclusions: The incidence of MCADD in Zibo city seems to be higher than that in other areas in China. The ACADM gene mutations c.449_452del (p.T150Rfs*4) and c.387+1delG are common, and a new mutation c.1076C>T (p.A359V) has been detected. No phenotype-genotype correlation has been found. Early diagonsis and treatment are effective measures to reduce poor prognosis.
Key words: Medium-chain acyl-CoA dehydrogenase deficiency    ACADM gene    Neonatal screening    Follow-up studies    Prognosis
收稿日期: 2022-03-21 出版日期: 2022-09-21
CLC:  R722.11  
通讯作者: 崔艳国     E-mail: cygdlp@126.com
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董丽萍
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引用本文:

董丽萍,季婵婵,许佳,崔艳国. 山东省淄博市241 297名新生儿中链酰基辅酶A脱氢酶缺乏症筛查及随访结果分析[J]. 浙江大学学报（医学版）, 2022, 51(3): 284-289.

DONG Liping,JI Chanchan,XU Jia,CUI Yanguo. Screening and follow-up results of neonate medium-chain acyl-CoA dehydrogenase deficiency in Zibo, Shandong province. J Zhejiang Univ (Med Sci), 2022, 51(3): 284-289.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0114    或    https://www.zjujournals.com/med/CN/Y2022/V51/I3/284

例序

性别

C0（μmol/L）

C8（μmol/L）

C8/C10

随访时间（月）

临床表现　

初筛

复筛

随访中位数

初筛

复筛

随访中位数

初筛

复筛

随访中位数

1

女

20.79

35.58

34.13

3.88

2.33

3.18

18.48

12.94

11.05

60

未见异常

2

女

28.24

20.62

21.36

1.76

3.51

3.23

16.00

19.50

18.51

48

低血糖昏迷1次

3

男

30.90

36.93

32.30

0.76

0.69

0.72

4.47

3.83

2.67

54

未见异常

4

女

29.23

23.79

30.21

2.58

0.75

1.96

10.32

5.76

5.08

13

未见异常

5

男

20.89

32.70

23.60

2.67

5.50

3.90

15.70

17.74

18.30

2

未见异常

6

女

46.17

—

—

26.83

—

—

9.75

—

—

—

围产期死亡
表 1  六例MCADD患儿串联质谱法检测及随访结果
图 1  一例死亡患儿c.467G>A Sanger测序结果A：例6父亲；B：例6母亲；C：例6；D：下一胎胎儿.

例 序

突变位点1

突变位点2

区域

核苷酸改变

氨基酸改变

致病风险

来 源

区域

核苷酸改变

氨基酸改变

致病风险

来源

1

内含子5

c.387+1delG

—

致病

母亲

外显子11

c.1189T>A

p.Y397N

致病

父亲

2

外显子11

c.1085G>A

p.G362E

致病

母亲

外显子11

c.1085G>A

p.G362E

致病

未检出

3

外显子11

c.1076C>T

p.A359V

临床意义未明

母亲

外显子11

c.1076C>T

p.A359V

临床意义未明

未检出

4

外显子6

c.449_452del

p.T150Rfs*4

致病

母亲

内含子5

c.388-19T>A

—

可能致病

父亲

5

内含子5

c.387+1delG

—

致病

母亲

外显子6

c.449_452del

p.T150Rfs*4

致病

父亲

6

外显子6

c.467G>A

p.C156Y

临床意义未明

母亲

外显子11~12

1p31.1(?_76226805_76229363_?)×1

—

可能致病

父亲
表 2  六例MCADD患儿基因突变特点
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