Newborn screening for mucopolysaccharidoses: Measurement of glycosaminoglycans by LC-MS/MS.

Autor:	Stapleton M; Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States of America.; Department of Biological Sciences, University of Delaware, Newark, DE, United States of America., Kubaski F; Medical Genetics Service, HCPA, Department of Genetics and Molecular Biology-PPGBM, UFRGS, INAGEMP, Porto Alegre, Brazil., Mason RW; Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States of America.; Department of Biological Sciences, University of Delaware, Newark, DE, United States of America., Shintaku H; Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan., Kobayashi H; Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan., Yamaguchi S; Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan., Taketani T; Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan., Suzuki Y; Medical Education Development Center, Gifu University, Japan., Orii K; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan., Orii T; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan., Fukao T; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan., Tomatsu S; Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States of America.; Department of Biological Sciences, University of Delaware, Newark, DE, United States of America.; Department of Pediatrics, Shimane University Faculty of Medicine, Shimane, Japan.; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, United States of America.
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2020 Jan 10; Vol. 22, pp. 100563. Date of Electronic Publication: 2020 Jan 10 (Print Publication: 2020).
DOI:	10.1016/j.ymgmr.2019.100563
Abstrakt:	Mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders which can lead to degenerative and irreversible skeletal, cardiovascular, pulmonary, and neurological damage. Current treatments, including hematopoietic stem cell transplantation and enzyme replacement therapy, have been found most effective if administered before clinical symptoms are present, highlighting the urgent need for the development of newborn screening. This study analyzed 18,222 dried blood spot samples from newborns for both enzyme activity and glycosaminoglycan (GAG) concentration levels. GAG levels were measured using liquid chromatography tandem mass spectrometry. Results were compared to our previously established cutoff values for three subtypes of GAGs: dermatan sulfate (DS) and heparan sulfate (HS0S and HSNS). Samples that were high for two of the three GAGs were identified and screened a second time. Samples were also measured for iduronate-2-sulfatase and alfa-L-iduronidase activity. A total of 300 samples were above the established cutoff values for at least two of the three GAGs after the first screening. One sample was determined through clinical and genetic testing to be a true positive for MPS II. The false positive rate after the first GAG screening was 1.64%. A Cochran's formula test showed that the samples available for the second screening were representative samples (p = .0000601). False positive rate after second GAG screening, extrapolated from the representative sample was 0.4%. False positive rate after enzyme activity assay by fluorimetry for IDUA and IDS enzymes was 0.21% and 0.18%. A combination of GAG and enzyme assays provided no false positive and false negative samples. Two-tier screening involving a combination of enzyme activity and multiple GAGs should be considered the gold standard for the diagnosis of MPS patients. (© 2020 The Authors.)
Databáze:	MEDLINE
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