Pseudodeficiency alleles affect the newborn screening of glycogen storage disease typeⅡ
10.3760/cma.j.issn.1009-9158.2019.12.011
- VernacularTitle: 假性缺陷等位基因影响糖原贮积病Ⅱ型的新生儿筛查
- Author:
Ting CHEN
1
;
Wenjuan QIU
;
Yu SUN
;
Jianguo WANG
;
Zhuwen GONG
;
Yu WANG
;
Xiaolan GAO
;
Yongguo YU
;
Xuefan GU
Author Information
1. Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Publication Type:Journal Article
- Keywords:
Glycogen storage disease type II;
Acid alpha-glucosidase;
Pseudodeficiency alleles;
Neonatal screening;
Dried blood spot testing;
Luminescent measurements
- From:
Chinese Journal of Laboratory Medicine
2019;42(12):1031-1036
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of pseudodeficiency alleles on the newborn screening of glycogen storage disease type Ⅱ(GSDⅡ) by using afluorometric enzymatic assay to determine acid α-glucosidase (GAA) activity in dried blood spot (DBS).
Methods:A total of 30 507 newborns′ DBSs, obtained from Newborn Screening Center of Xinhua Hospital Shanghai Jiao Tong University School of Medicine from May to December 2017, were screened for GSD Ⅱ by fluorometric enzymatic assay of GAA activity. The suspected positive DBSs after the first and second screening were directly analyzed by Sanger sequencing of GAA to confirm the diagnosis. Retrospective analysis of 3 172 controls without GSDⅡand 36 GSD Ⅱ patients were conducted to investigate the carrier status of pseudodeficiency alleles. Statistical analysis of frequency of pseudodeficiency alleles were carried out by Chi-square test or Fisher exact probability test.
Results:GAA activity of 30 507 newborns showed a positively skewed distribution.Twenty-nine cases of newborns, suspected to be GSDⅡwere confirmed to be normal with genetic analysis of the original DBSs. Among the 29 suspected positive cases, 24 cases were homozygous for pseudodeficiency alleles c.[1726A/A; 2065A/A], and the other 5 cases were c.[1726G/A; 2065G/A] heterozygote. The frequency of c.1726G>Ahomozygote in 3 172 non-GSD Ⅱcontrols was 2.08% (66/3 172), and c.1726G>A homozygote occurred in allelic conjunction with c.2065G>Ahomozygote. Frequency of c.[1726A; 2065A] haplotype in 3 172 controls was 3.2%(206/6 344). Frequency of c.[1726A/A; 2065A/A] homozygote in 36 GSDⅡpatients (16.67%, 6/36) was significantly higher than that in non-GSD Ⅱcontrols(2.08%, 66/3 172) (χ2=34.517, P<0.001).
Conclusions:Pseudodeficiency alleles show a high frequency in Chinese, which leads to a high false positive rate in the newborns screening of GSDⅡ.The afterword genetic analysis of the original DBS after the GAA activity screening could reduce the effect of pseudodeficiency alleles on the newborns screening of GSDⅡ.
