Test Id : MPS2B

If the patient has abnormal newborn screening results for mucopolysaccharidosis type II (MPS II), timely action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)

For more information see Newborn Screen Follow-up for Mucopolysaccharidosis Type II.

This test is recommended for assessment of newborns and infants with a positive newborn screen for mucopolysaccharidosis type II (MPS II). This test is not intended to be used as a monitoring test for individuals with confirmed MPS II.

Quantitative values of the glycosaminoglycans, dermatan and heparan sulfate, are not provided with this assay. If quantitative values are desired, order MPSBS / Mucopolysaccharides, Blood Spot.

This test is also available as a part of a reflex panel; see MPS2R / Endogenous Mucopolysaccharidosis Type II (I2S [Iduronate-2-Sulfatase]) Biomarker Reflex, Blood Spot.

Specimens stored at ambient temperatures for more than 13 days after collection may result in false-positive results in carrier and other unaffected individuals.

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Blood Spot Collection Card

Acceptable: Whatman Protein Saver 903 paper, PerkinElmer 226 filter paper, Munktell filter paper, local newborn screening card, postmortem screening card, or blood collected in tubes containing ACD or EDTA and dried on filter paper.

Specimen Volume: 2 Blood spots

Collection Instructions

1. An alternative blood collection option for patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Completely fill at least 2 circles on filter paper card (approximately 100 microliters blood per circle).

3. Let blood dry on filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

4. Do not expose specimen to heat or direct sunlight.

5. Do not stack wet specimens.

6. Keep specimen dry.

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

• Biochemical Genetics Patient Information
• Blood Spot Collection Card-Spanish Instructions
• Blood Spot Collection Card-Chinese Instructions
• Blood Spot Collection Instructions
• Newborn Screening Follow-up for Mucopolysaccharidosis type II

Biochemical Genetics Patient Information (T602)

1 Blood spot

Second-tier testing of newborns with an abnormal primary screening result for mucopolysaccharidosis type II (MPS II, decreased iduronate-2-sulfatase)

Follow-up testing for evaluation of an abnormal newborn screening result for MPS II

This test is not useful a monitoring test for individuals with MPS II.

This test is not appropriate for carrier detection.

This test is a second-tier assay for newborns and infants who have abnormal newborn screening results for mucopolysaccharidosis type II (MPS II) with reduced iduronate-2-sulfatase activity.

If the patient has abnormal newborn screening results for mucopolysaccharidosis type II (MPS II), timely action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)

For more information see Newborn Screen Follow-up for Mucopolysaccharidosis Type II.

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked lysosomal disorder caused by the deficiency of iduronate-2-sulfatase enzyme due to variants in the IDS gene. 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 male patients 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.

Individuals with MPS II typically demonstrate elevated levels of the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate (see MPSQU / Mucopolysaccharides Quantitative, Random, Urine; or MPSBS / Mucopolysaccharides, Blood Spot), as well as elevated levels of GAG fragments known as endogenous disaccharide biomarkers that are specific to the deficiency of iduronate-2-sulfatase. Reduced or absent activity of iduronate-2-sulfatase (see I2SWB / Iduronate-2-Sulfatase, Leukocytes) can confirm a diagnosis of MPS II but may also be deficient in unaffected individuals with pseudodeficiency as well as 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).

An interpretive report will be provided.

The qualitative measurement of mucopolysaccharidosis type II (MPS II) specific endogenous biomarkers is compared to the reference value. This report is in text form only, indicating if the MPS II specific endogenous biomarker value is or is not suggestive of a biochemical diagnosis of MPS II. Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis, independent biochemical (ie, in vitro enzyme assay and quantitative glycosaminoglycan measurement) or molecular genetic analyses are required, many of which are offered within Mayo Clinic Laboratories. Recommendations for additional biochemical testing and confirmatory studies (biomarker, enzyme assay, molecular analysis) are provided in the interpretative report.

Individuals with multiple sulfatase deficiency may also have abnormal levels of mucopolysaccharidosis type II specific biomarker.

1. ACMG Newborn Screening ACT Sheets. Newborn Screening ACT Sheet [Iduronate 2-Sulfatase Deficiency] Mucopolysaccharidosis Type II. American College of Medical Genetics and Genomics; 2022. Accessed October 23, 2024. Available at www.acmg.net/PDFLibrary/MPS-II.pdf

2. Saville JT, Herbst ZM, Gelb MH, Fuller M: Endogenous, non-reducing end glycosaminoglycan biomarkers for the mucopolysaccharidoses: Accurate diagnosis and elimination of false positive newborn screening results. Mol Gen Metab. 2023;140(3):107685.

3. Herbst ZM, Hong X, Urdaneta L, et al. Endogenous, non-reducing end glycosaminoglycan biomarkers are superior to internal disaccharide glycosaminoglycan biomarkers for newborn screening of mucopolysaccharidoses and GM1 gangliosidosis. Mol Genet Metab. 2023;140(1-2):107632

4. Herbst ZM, Urdaneta L, Klein T, Fuller M, Gelb MH. Evaluation of multiple methods for quantification of glycosaminoglycan biomarkers in newborn dried blood spots from patients with severe and attenuated mucopolysaccharidosis-I. Int J Neonatal Screen. 2020;6(3):69

Sample preparation consists of extraction from dried blood spots using aqueous buffer and the addition of reagents to aid in removing the analytes from the filter paper. The resulting extracted analytes are chemically derived to aid in chromatographic separation and to increase signal intensity. A liquid/liquid extraction is preformed to remove the derived analytes from bulk matrix. The sample is then analyzed via liquid chromatography tandem mass spectrometry.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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