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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Novel Phenotypic Insights into the IDS c.817C>T Variant in Mucopolysaccharidosis Type II from Newborn Screening Cohorts

by
Éliane Beauregard-Lacroix
1,
Caitlin Menello
1,
Madeline Steffensen
1,
Hsiang-Yu Lin
2,3,
Chih-Kuang Chuang
2,
Shuan-Pei Lin
2,3 and
Can Ficicioglu
1,4,*
1
Section of Biochemical Genetics, Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
2
Department of Pediatrics, Medical Research and International Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan
3
Department of Medicine, MacKay Medical University, New Taipei City 25245, Taiwan
4
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Int. J. Neonatal Screen. 2025, 11(3), 68; https://doi.org/10.3390/ijns11030068
Submission received: 18 July 2025 / Revised: 20 August 2025 / Accepted: 22 August 2025 / Published: 26 August 2025
(This article belongs to the Special Issue Advances in Newborn Screening for Lysosomal Disorders: From Laboratory Screening to Diagnosis)
Versions Notes

Abstract

Mucopolysaccharidosis (MPS) type II, or Hunter syndrome, is an X-linked lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase. Glycosaminoglycan (GAG) accumulation leads to progressive multisystemic involvement, with coarse facial features, hepatosplenomegaly, short stature, recurrent upper respiratory infections, hearing loss, hernias, dysostosis multiplex, joint contractures, and cardiac valve disease. Individuals with the neuronopathic form of the disease also have central nervous system (CNS) involvement with developmental delay and progressive cognitive decline. Enzyme replacement therapy (ERT), idursulfase, is the only FDA-approved treatment for MPS II. MPS II was added to the Recommended Uniform Screening Panel (RUSP) in the United States in 2022, and screening is ongoing in several other countries, including Taiwan. Here, we report seven individuals from four families identified through newborn screening sharing the same IDS variant: c.817C>T, p.Arg273Trp. Confirmatory testing demonstrated low iduronate-2-sulfatase activity level and elevated GAGs in every individual, but they had no signs or symptoms of MPS II. They were aged 8 months to 60 years old according to the most recent assessment and all remained asymptomatic. ERT was not initiated for any of them. Our findings suggest that the IDS c.817C>T variant is associated with abnormal biochemical findings but no clinical phenotype of MPS II. Newborn screening will likely identify additional cases and provide a better understanding of the clinical significance of this variant.
Keywords: mucopolysaccharidosis type II; Hunter syndrome; lysosomal storage disease; newborn screening mucopolysaccharidosis type II; Hunter syndrome; lysosomal storage disease; newborn screening

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MDPI and ACS Style

Beauregard-Lacroix, É.; Menello, C.; Steffensen, M.; Lin, H.-Y.; Chuang, C.-K.; Lin, S.-P.; Ficicioglu, C. Novel Phenotypic Insights into the IDS c.817C>T Variant in Mucopolysaccharidosis Type II from Newborn Screening Cohorts. Int. J. Neonatal Screen. 2025, 11, 68. https://doi.org/10.3390/ijns11030068

AMA Style

Beauregard-Lacroix É, Menello C, Steffensen M, Lin H-Y, Chuang C-K, Lin S-P, Ficicioglu C. Novel Phenotypic Insights into the IDS c.817C>T Variant in Mucopolysaccharidosis Type II from Newborn Screening Cohorts. International Journal of Neonatal Screening. 2025; 11(3):68. https://doi.org/10.3390/ijns11030068

Chicago/Turabian Style

Beauregard-Lacroix, Éliane, Caitlin Menello, Madeline Steffensen, Hsiang-Yu Lin, Chih-Kuang Chuang, Shuan-Pei Lin, and Can Ficicioglu. 2025. "Novel Phenotypic Insights into the IDS c.817C>T Variant in Mucopolysaccharidosis Type II from Newborn Screening Cohorts" International Journal of Neonatal Screening 11, no. 3: 68. https://doi.org/10.3390/ijns11030068

APA Style

Beauregard-Lacroix, É., Menello, C., Steffensen, M., Lin, H.-Y., Chuang, C.-K., Lin, S.-P., & Ficicioglu, C. (2025). Novel Phenotypic Insights into the IDS c.817C>T Variant in Mucopolysaccharidosis Type II from Newborn Screening Cohorts. International Journal of Neonatal Screening, 11(3), 68. https://doi.org/10.3390/ijns11030068

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