短链酰基辅酶A脱氢酶缺乏症新生儿筛查、临床特征及基因突变分析

黄新文; 张玉; 杨建滨; 洪芳; 钱古柃; 童凡; 毛华庆; 黄晓磊; 周雪莲; 杨茹莱; 赵正言

doi:10.3760/cma.j.issn.0578-1310.2016.12.011

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中华儿科杂志

• 临床研究与实践 •

ENGLISH ABSTRACT

短链酰基辅酶A脱氢酶缺乏症新生儿筛查、临床特征及基因突变分析

作者及单位信息

出版日期： 2016 -12 -02 ·

DOI： 10.3760/cma.j.issn.0578-1310.2016.12.011

Clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency by neonatal screening

Authors Info & Affiliations

Huang Xinwen

Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China

Zhang Yu

Yang Jianbin

Hong Fang

Qian Gulin

Tong Fan

Mao Huaqing

Huang Xiaolei

Zhou Xuelian

Yang Rulai

Zhao Zhengyan

Published： 2016 -12 -02 ·

DOI： 10.3760/cma.j.issn.0578-1310.2016.12.011

5005

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摘要

目的了解新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)患病率、临床特征及基因突变特点。

方法采用串联质谱技术，对2009年1月到2015年10月1 430 024例新生儿进行遗传代谢病筛查，对筛查出的疑似SCADD患儿通过尿有机酸分析，酰基辅酶A脱氢酶编码基因(ACADS)进行确诊，对确诊病例分析其临床、生化改变及基因突变特点，进行饮食指导、生活管理及补充左旋肉碱，随访观察其生长及智能发育情况。

结果确诊SCADD 17例，患病率为1/84 117。患儿无临床症状，血丁酰基肉碱(C4)及其与乙酰基肉碱(C2)，丙酰基肉碱(C3)比值均增高，C4 0.71～3.14 μmol/L(正常值0.03～0.48 μmol/L)，C4/C2 0.07～0.23(正常值0.01～0.04)，C4/C3 0.65～2.04(正常值0.05～0.39)。尿有机酸分析13例，乙基丙二酸均增高[9.30～90.99 mg/g肌酐(正常值0～6.20 mg/g肌酐)]，1例伴甲基琥珀酸增高[12.33 mg/g肌酐(正常值0～6.40 mg/g肌酐)]，1例伴乙酰甘氨酸增高[3.52 mg/g肌酐(正常值0～0.70 mg/g肌酐)]。发现ACADS基因突变13种，其中12种为错义突变，1种为移码突变，均为已知突变。1例为纯合突变(c.1031A>G)，其余为复合杂合突变。常见突变为c.1031A>G(35.3%)与c.164C>T(20.6%)，ACADS基因型与乙基丙二酸以及C4浓度水平无明显相关。对患儿随访8～42个月，均未出现临床症状，体格及智力发育正常。

结论SCADD在新生儿人群中患病率为1/84 117。通过新生儿筛查确诊的SCADD无临床症状。常见基因突变为c.1031A>G与c.164C>T。

关键词：脂质代谢缺陷，先天性;酰基CoA脱氢酶;新生儿筛查

ABSTRACT

ObjectiveTo investigate the incidence, clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency (SCADD).

MethodFrom January, 2009 to October, 2015, a retrospective analysis of the urine organic acids and acyl-coenzyme A dehydrogenase (ACADS) gene mutation characteristics of patients diagnosed as SCADD by newborn screening using tandem mass spectrometry in Department of Genetics and Metabolism (Newborn screening Center of Zhejiang Province), Children's Hospital, Zhejiang University School of Medicine. Dietary guidance, life management and supplementation of L-carnitine were conducted, and growth and intelligence development were observed during follow-up among the SCADD patients.

ResultA total of 1 430 024 neonates, seventeen cases were diagnosed with SCADD with an incidence of 1/84 117. All patients had no clinical symptoms, and intelligence and physical development were normal. Blood butylacyl-carnitine (C4) levels and the ratios increased, C4 0.713.14 μmol/L(reference value 0.03-0.48 μmol/L), C4/C2 0.07-0.23(reference value 0.01-0.04), C4/C3 0.65-2.04(reference value 0.05-0.39). Thirteen with increased urinary ethyl malonic acid (9.30-90.99 mg/g creatinine (reference value 0-6.20 mg/g creatinine )), one patient was accompanied by increased methyl succinic acid (12.33 mg/g creatinine(reference value 0-6.40 mg/g creatinine)), one subject with increased acetylglycine (3.52 mg/g creatinine(reference value 0-0.70 mg/g creatinine)). A total of 13 known mutations were detected in the ACADS gene, 1 homozygous mutation (c.1031A>G), the others are compound heterozygous mutations. One frameshift mutation (c.508_509delGC) and 12 missense mutations were detected. Common mutation were c. 1031A>G(35.3%), c. 164C>T(20.6%) and c. 991G>A(11.8%). SCADD in newborn screening program had no clinical symptoms and normal growth development after 8-42 months follow-up.

ConclusionCases with SCADD had no clinical symptoms with an incidence of 1/84117. The c. 164C>T and c. 1031A>G may be the common mutations.

KEYWORDS： Lipid metabolism, inborn errors;Acyl-Co A dehydrogenase;Newborn screening

Corresponding author: Zhao Zhengyan, Email: nc.defudabe.ujzyzoahz

FUNDING:

National Natural Science Foundation of China(81172681)

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No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.

All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

黄新文,张玉,杨建滨,等. 短链酰基辅酶A脱氢酶缺乏症新生儿筛查、临床特征及基因突变分析[J]. 中华儿科杂志,2016,54(12)：927-930.

DOI:10.3760/cma.j.issn.0578-1310.2016.12.011

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短链酰基辅酶A脱氢酶缺乏症(Short-chain acyl-CoA dehydrogenase deficiency, SCADD; OMIM#201470)是酰基辅酶A脱氢酶编码基因(SCAD-encoding gene，ACADS)缺陷引起线粒体脂肪酸氧化代谢障碍的一种常染色体隐性遗传病。SCAD是丁酰基肉碱(C4)与己酰基肉碱线粒体β氧化脱氢的第一个催化酶 ^{[
1
]}，其活性缺陷会引起血C4、尿乙基丙二酸及甲基琥珀酸的蓄积 ^{[
2
]}，导致发育迟缓、低血糖、癫痫和行为异常等临床表现，也有研究发现通过新生儿筛查确诊的SCADD患者多数无临床表现 ^{[
3
,

4
]}。浙江大学医学院附属儿童医院遗传代谢科(浙江省新生儿疾病筛查中心)于2009年1月至2015年10月通过串联质谱进行新生儿遗传代谢病筛查，了解SCADD患病率、临床特征及基因突变特点。

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备注信息

通信作者：赵正言，Email： nc.defudabe.ujzyzoahz

基金项目：

国家自然科学基金 (81172681) 查看更多基金信息

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