[1]郑泉志,傅清流,彭维林,等.新生儿异戊酸血症串联质谱法与相关基因突变检测的价值研究[J].现代检验医学杂志,2022,37(05):61-64.[doi:10.3969/j.issn.1671-7414.2022.05.013]
　ZHENG Quan-zhi,FU Qing-liu,PENG Wei-lin,et al.Study on the Value of Tandem Mass Spectrometry and Related Gene Mutation Detection in Neonates with Isovaleric Acidemia[J].Journal of Modern Laboratory Medicine,2022,37(05):61-64.[doi:10.3969/j.issn.1671-7414.2022.05.013]
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新生儿异戊酸血症串联质谱法与相关基因突变检测的价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年05期
页码:
61-64
栏目:
论著
出版日期:
2022-09-15

文章信息/Info

Title:
Study on the Value of Tandem Mass Spectrometry and Related Gene Mutation Detection in Neonates with Isovaleric Acidemia
文章编号:
1671-7414（2022）05-061-04
作者:
郑泉志; 傅清流; 彭维林; 林壹明
泉州市妇幼保健院·儿童医院检验科，福建泉州 362000
Author(s):
ZHENG Quan-zhi; FU Qing-liu;  PENG Wei-lin;  LIN Yi-ming
Department of Clinical Laboratory ，Quanzhou Woman’s and Children’s Hospital, Fujian Quanzhou 362000, China
关键词:
异戊酸血症; 新生儿筛查; 串联质谱技术; 异戊酰辅酶A 脱氢酶基因
分类号:
R722.11；Q503
DOI:
10.3969/j.issn.1671-7414.2022.05.013
文献标志码:
A
摘要:
目的　了解福建省泉州地区新生儿异戊酸血症（isovaleric acidemia, IVA）串联质谱法与相关基因突变检测情况。方法　2019 年1 月～ 2020 年12 月，泉州地区共有151 917 例新生儿进行串联质谱遗传代谢病筛查，异戊酰基肉碱(isovalerylcarnitine, AISO-C5 ) 浓度升高的筛查样本应用MassARRAY 技术进行IVD 基因突变筛查，IVA 疑似样本采用高通量测序技术诊断。结果　研究期间共有132 例新生儿表现为浓度升高，采用传统筛查规则需召回132 例新生儿，召回复查阳性人数20 例，1 例确诊为IVA 患者，IVA 的阳性预测值为0.76%。此外，3 例新生儿被诊断为2- 甲基丁酰辅酶A 脱氢酶缺乏症（2-methylbutyryl-CoA dehydrogenase deficiency，2-MBAD）患者。联合应用基因突变筛查后，仅5 例新生儿结果异常，基因诊断证实4 例新生儿为IVA 携带者，1 例新生儿为IVA 患者，因此IVA 的阳性预测值提高至20%。所有患者的新生儿筛查和召回复查结果均显示AISO-C5 浓度升高。1 例IVA 患者携带IVD 基因c.499A > G(p.M167V) 和c.1208A > G（p.Y403C）复合杂合突变，3 例2-MBAD 患者均携带ACADSB 基因c.1165A > G (p.M389V)纯合突变。结论　联合应用MassARRAY 技术进行IVD 基因突变筛查可以有效排除AISO-C5 升高的假阳性标本，提高阳性预测值，明显提高IVA 的新生儿筛查效率。
Abstract:
Objective　To investigate the value of tandem mass spectrometry and related gene mutation detection of neonates with isovaleric acidemia (IVA) in Quanzhou of Fujian Province. Methods　From January 2019 to December 2020, a total of 151 917 newborns in Quanzhou were screened for inherited metabolic diseases by tandem mass spectrometry (MS/MS). Newborns with elevated levels of isovalerylcarnitine (AISO-C5 ) were subjected to IVD gene mutation screening using MassARRAY assay, and suspected patients were diagnosed by second-generation sequencing. Results　During the study period, 132 newborns with elevated AISO-C5 levels had to be recalled by conventional MS/MS screening, of which 20 were still positive when recalled, and one patient was confirmed as IVA. The positive predictive value of IVA was 0.76%. In addition, three neonates were diagnosed with 2-methylbutyryl-CoA dehydrogenase deficiency (2-MBAD). After the application of mutation screening, only 5 newborns had abnormal genetic screening results, and the genetic analysis confirmed that four newborns were IVA carriers and one patient newborn was IVA, so the positive predictive value of IVA was increased to 20%. The NBS results showed that all patients with increased concentrations of AISO-C5 , and the AISO-C5 concentration was still elevated during recall. The IVA patient carried the compound heterozygous mutation of c.499A > G (p.P167V) and c.1208A >G (p.Y403C) in the IVD gene, and all three 2-MBAD patients carried the homozygous mutation of c.1165A > G (p.M389V) in the ACADSB gene. Conclusion　The application of MassARRAY assay for IVD gene mutation screening could effectively eliminate AISO-AISO-C5 false positive samples and increase the positive predictive value, thus significantly improved the efficiency of newborn screening for IVA.

参考文献/References:

[1] LI Yanhan, SHEN Ming, JIN Ying, et al. Eight novel mutations detected from eight Chinese patients with isovaleric acidemia[J]. Clinica Chimica Acta, 2019,498: 116-121.
[2] SZYMA?SKA E, JEZELA-STANEK A, BOGDA?SKA A, et al. Long term follow-up of polish patients with isovaleric aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria[J].Diagnostics (Basel), 2020,10(10):738.
[3] M?TZE U, HENZE L, GLEICH F, et al. Newborn screening and disease variants predict neurological outcome in isovaleric aciduria[J]. Journal of Inherited Metabolic Disease, 2021, 44(4): 857-870.
[4] 钟锦平, 傅清流, 林壹明. 福建省泉州地区新生儿有机酸血症的发病率与疾病谱筛查结果分析[J]. 现代检验医学杂志, 2019, 34(5):52-55.
ZHONG Jinping, FU Qingliu, LIN Yiming. Systematic analysis of the incidence and disease spectrum of organic academia newborn screening results in Quanzhou,Fujian Province[J].Journal of Modern Laboratory Medicine, 2019, 34(5):52-55.
[5] 钟锦平, 彭维林, 傅清流, 等. 福建泉州地区新生儿氨基酸代谢障碍的筛查结果分析[J]. 现代检验医学杂志, 2020, 35(4):41-44, 78.
ZHONG Jinping, PENG Weilin, FU Qingliu et al.Retrospective analysis of the neonatal screening results of amino acid disorders in Quanzhou Region, Fujian Province [J].Journal of Modern Laboratory Medicine,2020, 35(4):41-44, 78.
[6] 刘芙蓉, 王兴, 孙小红, 等.甘肃省正常新生儿干血斑氨基酸及酰基肉碱串联质谱检测指标医学参考范围的调查[J].现代检验医学杂志, 2018, 33（2）：31-34, 37.
LIU Furong, WANG Xing, SUN Xiaohong, et al.Investigation on the medical reference range of the normal neonates with the amino Acid and Acyl carnitine tandem mass spectrometry in Gansu Province[J].Journal of Modern Laboratory Medicine, 2018,33(2):31-34,37.
[7] SCHLUNE A, RIEDERER A, MAYATEPEK E, et al.Aspects of newborn screening in isovaleric acidemia[J].International Journal of Neonatal Screening, 2018, 4(1):7.
[8] LIN Yiming, GAO Hongzhi, LIN Chunmei, et al.Biochemical,clinical,and genetic characteristics of short/branched chain Acyl-CoA dehydrogenase deficiency in Chinese patients by newborn screening[J].Front Genet, 2019, 10:802.
[9] LIN Yiming, CHEN Dongmei, PENG Weilin, et al. Newborn screening for isovaleric acidemia in Quanzhou, China[J]. Clinica Chimica Acta, 2020, 509:25-29.
[10] 胡真真, 杨建滨, 胡凌微, 等. 浙江省新生儿异戊酸血症筛查及临床分析[J]. 浙江大学学报（医学版）,2020, 49(5):556-564.
HU Zhenzhen, YANG Jianbin, HU Lingwei, et al.Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang Province [J].Journal of Zhejiang University(Medical Sciences), 2020, 49(5):556-564.
[11] WU Fang, FAN Sujuan, ZHOU Xihui. Neonatal isovaleric acidemia in China: A case report and review of literature[J]. World Journal of Clinical Cases, 2021,9(2): 436-444.
[12] CARLING R S, BURDEN D, HUTTON I, et al.Introduction of a simple second tier screening test for AISO-C5 isobars in dried blood spots: reducing the false positive rate for isovaleric acidaemia in expanded newborn screening[J]. JIMD Reports, 2018, 38: 75-80.
[13] MINKLER P E, STOLL M S K, INGALLS S T, et al. Selective and accurate AISO-C5 acylcarnitine quantitation by UHPLC-MS/MS: Distinguishing true isovaleric acidemia from pivalate derived interference[J]. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences, 2017, 1061-1062: 128-133.
[14] PORTA F, CHIESA N, MARTINELLI D, et al.Clinical, biochemical, and molecular spectrum of short/branched-chain Acyl-CoA dehydrogenase deficiency:two new cases and review of literature[J]. Journal of Pediatric Endocrinology & Metabolism, 2019, 32(2):101-108.

备注/Memo

备注/Memo:
基金项目：福建省卫生健康科技计划项目（2020QNA083）：异戊酸血症的二阶基因筛查。
作者简介：郑泉志（1978-），男，本科，副主任技师，研究方向为临床检验学，E-mail: 78334180qq.com。
通讯作者：林壹明（1987-），男，硕士，主管技师，研究方向为医学遗传学，E-mail: linyiming0819@sina.com。
更新日期/Last Update: 2022-09-15