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Test Catalog

Test ID: I2SBS    
Iduronate-2-Sulfatase, Blood Spot

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of mucopolysaccharidosis II (MPS II, Hunter syndrome) using dried blood spot specimens

 

This test is not useful for determining carrier status for MPS II.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test provides diagnostic testing for individuals with positive newborn screen results or clinical signs and symptoms suspicious for mucopolysaccharidosis type II (MPS II, Hunter syndrome).

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate, also known as glycosaminoglycans (GAG). Accumulation of GAG in the lysosomes interferes with normal functioning of cells, tissues, and organs. Mucopolysaccharidosis II, (MPS II, Hunter syndrome) is an X-linked lysosomal storage disorder caused by the deficiency of iduronate sulfatase (IDS) enzyme and gives rise to the physical manifestations of the disease.

 

Clinical features and severity of symptoms are widely variable ranging from severe infantile onset disease to an attenuated form, which generally has a later onset with a milder clinical presentation. Symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, and profound neurologic involvement leading to developmental delays and regression. As an X-linked disorder, MPS II occurs primarily in males with an estimated incidence of 1 in 120,000 male births, although symptomatic carrier females have been reported. Treatment availability, including hematopoietic stem cell transplantation and enzyme replacement therapy, makes early diagnosis desirable, as early initiation of treatment has been shown to improve clinical outcomes. Newborn screening for MPS II has been implemented in some states.

 

A diagnostic workup in an individual with MPS II typically demonstrates elevated levels of urinary glycosaminoglycans and increased amounts of both dermatan and heparan sulfate (see MPSQU / Mucopolysaccharides Quantitative, Random, Urine and MPSBS / Mucopolysaccharides, Blood Spot). Reduced or absent activity of IDS can confirm a diagnosis of MPS II but may also be deficient in individuals with multiple sulfatase deficiency. Enzymatic testing is not reliable to detect carriers. Molecular genetic testing of the IDS gene allows for detection of the disease-causing variant in affected patients and subsequent carrier detection in female relatives (see MPS2Z / Hunter Syndrome, Full Gene Analysis, Varies). Currently, no clear genotype-phenotype correlations have been established.(1)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

> or =1.5 nmol/hour/mL

Interpretation Provides information to assist in interpretation of the test results

Results below 1.5 nmol/hour/mL in properly submitted specimens are consistent with iduronate-2-sulfatase deficiency (mucopolysaccharidosis II: MPS II, Hunter syndrome). If clinically indicated, consider further confirmation by molecular genetic analysis of the IDS gene. Note that this enzyme's activity can also be reduced in multiple sulfatase deficiency (MSD).(2) If clinically indicated, consider biochemical genetic testing of other sulfatases or molecular genetic testing of the SUMF1 gene to exclude MSD.

 

Normal results (> or =1.5 nmol/hour/mL) are not consistent with iduronate-2-sulfatase deficiency.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The presence of a pseudodeficiency allele may cause reduced activity of iduronate sulfatase in the artificial substrate used in this assay.

 

Enzyme levels may be normal in individuals receiving enzyme replacement therapy or who have undergone bone marrow transplant.

 

Iduronate-2-sulfatase can also be deficient in individuals with multiple sulfatase deficiency.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. D’Avanzo F, Rigon L, Zanetti A, Tomanin R: Mucopolysaccharidosis type II: One hundred years of research, diagnosis, and treatment. Int J Mol Sci. 2020 Feb;21(4):1258. doi: 10.3390/ijms21041258 2. Hopwood JJ, Ballabio A. Multiple sulfatase deficiency and the nature of the sulfatase family. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed February 11, 2021. https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225546905

3. Neufeld EF, Muenzer J: The Mucopolysaccharidoses. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed April 9, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookId=2709&sectionId=225544161

4. Scarpa M: Mucopolysaccharidosis Type II. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2007. Updated October 4, 2018. Accessed February 11, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1274/

Special Instructions Library of PDFs including pertinent information and forms related to the test