An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan
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 c...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/9/4/140 |
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| author | Hsiang-Yu Lin Chung-Lin Lee Yun-Ting Lo Ru-Yi Tu Ya-Hui Chang Chia-Ying Chang Pao Chin Chiu Tung-Ming Chang Wen-Hui Tsai Dau-Ming Niu Chih-Kuang Chuang Shuan-Pei Lin |
| author_facet | Hsiang-Yu Lin Chung-Lin Lee Yun-Ting Lo Ru-Yi Tu Ya-Hui Chang Chia-Ying Chang Pao Chin Chiu Tung-Ming Chang Wen-Hui Tsai Dau-Ming Niu Chih-Kuang Chuang Shuan-Pei Lin |
| author_sort | Hsiang-Yu Lin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T07:42:33Z |
| format | Article |
| id | doaj.art-a5cc66bb91bb4e7bb710cfa83c3f4173 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-12-10T07:42:33Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-a5cc66bb91bb4e7bb710cfa83c3f41732022-12-22T01:57:17ZengMDPI AGDiagnostics2075-44182019-10-019414010.3390/diagnostics9040140diagnostics9040140An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in TaiwanHsiang-Yu Lin0Chung-Lin Lee1Yun-Ting Lo2Ru-Yi Tu3Ya-Hui Chang4Chia-Ying Chang5Pao Chin Chiu6Tung-Ming Chang7Wen-Hui Tsai8Dau-Ming Niu9Chih-Kuang Chuang10Shuan-Pei Lin11Department of Medicine, MacKay Medical College, New Taipei City 252, TaiwanDepartment of Pediatrics, MacKay Memorial Hospital, Hsinchu 300, TaiwanDepartment of Laboratory Medicine, MacKay Memorial Hospital, Taipei 100, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei 100, TaiwanDepartment of Pediatrics, MacKay Memorial Hospital, Taipei 100, TaiwanDepartment of Pediatrics, MacKay Memorial Hospital, Hsinchu 300, TaiwanDepartment of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 800, TaiwanDepartment of Pediatric Neurology, Changhua Christian Children’s Hospital, Changhua 500, TaiwanDepartment of Pediatrics, Chi Mei Medical Center, Tainan 700, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 100, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei 100, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City 252, TaiwanBackground: 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.https://www.mdpi.com/2075-4418/9/4/140cross-specialty collaborationglycosaminoglycanshigh-risk screeningliquid chromatography/tandem mass spectrometrymucopolysaccharidosis |
| spellingShingle | Hsiang-Yu Lin Chung-Lin Lee Yun-Ting Lo Ru-Yi Tu Ya-Hui Chang Chia-Ying Chang Pao Chin Chiu Tung-Ming Chang Wen-Hui Tsai Dau-Ming Niu Chih-Kuang Chuang Shuan-Pei Lin An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan Diagnostics cross-specialty collaboration glycosaminoglycans high-risk screening liquid chromatography/tandem mass spectrometry mucopolysaccharidosis |
| title | An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan |
| title_full | An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan |
| title_fullStr | An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan |
| title_full_unstemmed | An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan |
| title_short | An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan |
| title_sort | at risk population screening program for mucopolysaccharidoses by measuring urinary glycosaminoglycans in taiwan |
| topic | cross-specialty collaboration glycosaminoglycans high-risk screening liquid chromatography/tandem mass spectrometry mucopolysaccharidosis |
| url | https://www.mdpi.com/2075-4418/9/4/140 |
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