Newborn screening for mucopolysaccharidoses: Measurement of glycosaminoglycans by LC-MS/MS.
Publication/Presentation Date
3-1-2020
Abstract
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.
Volume
22
First Page
100563
Last Page
100563
ISSN
2214-4269
Published In/Presented At
Stapleton, M., Kubaski, F., Mason, R. W., Shintaku, H., Kobayashi, H., Yamaguchi, S., Taketani, T., Suzuki, Y., Orii, K., Orii, T., Fukao, T., & Tomatsu, S. (2020). Newborn screening for mucopolysaccharidoses: Measurement of glycosaminoglycans by LC-MS/MS. Molecular genetics and metabolism reports, 22, 100563. https://doi.org/10.1016/j.ymgmr.2019.100563
Disciplines
Medicine and Health Sciences
PubMedID
31956510
Department(s)
Fellows and Residents
Document Type
Article