標題: An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan
作者: Lin, Hsiang-Yu
Lee, Chung-Lin
Lo, Yun-Ting
Tu, Ru-Yi
Chang, Ya-Hui
Chang, Chia-Ying
Chiu, Pao Chin
Chang, Tung-Ming
Tsai, Wen-Hui
Niu, Dau-Ming
Chuang, Chih-Kuang
Lin, Shuan-Pei
生醫工程研究所
Institute of Biomedical Engineering
關鍵字: cross-specialty collaboration;glycosaminoglycans;high-risk screening;liquid chromatography;tandem mass spectrometry;mucopolysaccharidosis
公開日期: 1-Dec-2019
摘要: Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years-three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.
URI: http://dx.doi.org/10.3390/diagnostics9040140
http://hdl.handle.net/11536/153512
DOI: 10.3390/diagnostics9040140
期刊: DIAGNOSTICS
Volume: 9
Issue: 4
起始頁: 0
結束頁: 0
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