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

Authors :
Chih-Kuang Chuang
Yuan-Rong Tu
Chung-Lin Lee
Yun-Ting Lo
Ya-Hui Chang
Mei-Ying Liu
Hsin-Yun Liu
Hsiao-Jan Chen
Shu-Min Kao
Li-Yun Wang
Huey-Jane Ho
Hsiang-Yu Lin
Shuan-Pei Lin
Source :
International Journal of Molecular Sciences, Vol 23, Iss 17, p 9979 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
17
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.1fd735f3bfd4cdea047636d5b1cb7e6
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23179979