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Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance...

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Autores principales: Chuang, Chih-Kuang, Tu, Yuan-Rong, Lee, Chung-Lin, Lo, Yun-Ting, Chang, Ya-Hui, Liu, Mei-Ying, Liu, Hsin-Yun, Chen, Hsiao-Jan, Kao, Shu-Min, Wang, Li-Yun, Ho, Huey-Jane, Lin, Hsiang-Yu, Lin, Shuan-Pei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456254/
https://www.ncbi.nlm.nih.gov/pubmed/36077388
http://dx.doi.org/10.3390/ijms23179979
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author Chuang, Chih-Kuang
Tu, Yuan-Rong
Lee, Chung-Lin
Lo, Yun-Ting
Chang, Ya-Hui
Liu, Mei-Ying
Liu, Hsin-Yun
Chen, Hsiao-Jan
Kao, Shu-Min
Wang, Li-Yun
Ho, Huey-Jane
Lin, Hsiang-Yu
Lin, Shuan-Pei
author_facet Chuang, Chih-Kuang
Tu, Yuan-Rong
Lee, Chung-Lin
Lo, Yun-Ting
Chang, Ya-Hui
Liu, Mei-Ying
Liu, Hsin-Yun
Chen, Hsiao-Jan
Kao, Shu-Min
Wang, Li-Yun
Ho, Huey-Jane
Lin, Hsiang-Yu
Lin, Shuan-Pei
author_sort Chuang, Chih-Kuang
collection PubMed
description Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.
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spelling pubmed-94562542022-09-09 Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants Chuang, Chih-Kuang Tu, Yuan-Rong Lee, Chung-Lin Lo, Yun-Ting Chang, Ya-Hui Liu, Mei-Ying Liu, Hsin-Yun Chen, Hsiao-Jan Kao, Shu-Min Wang, Li-Yun Ho, Huey-Jane Lin, Hsiang-Yu Lin, Shuan-Pei Int J Mol Sci Article Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment. MDPI 2022-09-01 /pmc/articles/PMC9456254/ /pubmed/36077388 http://dx.doi.org/10.3390/ijms23179979 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chuang, Chih-Kuang
Tu, Yuan-Rong
Lee, Chung-Lin
Lo, Yun-Ting
Chang, Ya-Hui
Liu, Mei-Ying
Liu, Hsin-Yun
Chen, Hsiao-Jan
Kao, Shu-Min
Wang, Li-Yun
Ho, Huey-Jane
Lin, Hsiang-Yu
Lin, Shuan-Pei
Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title_full Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title_fullStr Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title_full_unstemmed Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title_short Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants
title_sort updated confirmatory diagnosis for mucopolysaccharidoses in taiwanese infants and the application of gene variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456254/
https://www.ncbi.nlm.nih.gov/pubmed/36077388
http://dx.doi.org/10.3390/ijms23179979
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