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

Int J Mol Sci. 2022 Sep 1;23(17):9979. doi: 10.3390/ijms23179979.

PMID: 36077388

Chih-Kuang Chuang, Yuan-Rong Tu, Chung-Lin Lee

Highlights: This study presents the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI.

Abstract

Background: A genetic abnormality known as mucopolysaccharidosis (MPS) is a lysosomal storage disorder that prevents the progressive breakdown of glycosaminoglycans (GAGs) because it lacks one particular enzyme activity. With the exception of MPS II, all other forms of MPS are autosomal recessive, meaning that two copies of a defective allele are required for the disease to manifest.

Objective: The status of variant alleles and the biochemical findings in newborns suspected of having MPS I, II, IVA, and VI are presented in this study.

Results: 324 suspected infants were enrolled, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation by newborn screening centers in Taiwan. One particular enzyme activity in dried blood spot filter paper from each of these infants was lower than the cut-off value in both the first blood sample and the subsequent follow-up sample. Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays were the confirmatory techniques used in this study. The findings revealed that five, nine, and six infants, respectively, had MPS I, II, and IVA, and they were all asymptomatic. Thus, a laboratory diagnosis is crucial to confirm the MPS diagnosis. The other infants were labeled as strongly suspected cases needing prolonged and thorough follow-up exams because of discovered nucleotide abnormalities and decreases in leukocyte enzyme activity.

Conclusion: In conclusion, analysis of genetic variants can help predict outcomes and direct treatment. The most potent biomarkers detected in urine, such as the quantification of GAG-derived disaccharides like dermatan sulfate, heparan sulfate, and keratan sulfate, are necessary for the final confirmation of MPS.

Keywords: GAG-derived disaccharide, X-linked recessive inheritance, autosomal recessive inheritance, glycosaminoglycan (GAG), mucopolysaccharidosis, variant allele