Test Id : MP8BS

Testing begins with screening for mucopolysaccharidoses. If results are normal or indicate mucopolysaccharidosis VII, testing is complete.

If results indicate mucopolysaccharidoses II, IIIA, IIIB, IIIC, IVA, IVB, or VI, quantitation of heparan sulfate, dermatan sulfate and keratan sulfate may be performed at an additional charge.

To evaluate newborn patients in follow-up to an abnormal newborn screen for MPSI, the recommended tests are IDUAW / Alpha-L-Iduronidase, Leukocytes and MPSBS / Mucopolysaccharidosis, Blood Spot, MPSWB / Mucopolysaccharidosis, Blood, MPSER / Mucopolysaccharides Quantitative, Serum or MPSQU / Mucopolysaccharides Quantitative, Random, Urine.

To evaluate newborn patients in follow-up to an abnormal newborn screen for MPSII, the recommended tests are I2SB / Iduronate-2-Sulfatase, Blood Spot or I2SWB / Iduronate-2-Sulfatase, Leukocytes and MPSBS / Mucopolysaccharidosis, Blood Spot, MPSWB / Mucopolysaccharidosis, Blood, MPSER / Mucopolysaccharides Quantitative, Serum or MPSQU / Mucopolysaccharides Quantitative, Random, Urine.

1. Patient's age is required.

2. Reason for testing is required

Submit only 1 of the following specimen types:

Preferred:

Specimen Type: Blood spot

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, 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 a patient 1 year of age or older is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. At least 2 spots should be complete (ie, unpunched).

3. Let blood dry on filter paper at room 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.

Specimen Stability Information: Refrigerated (preferred) 60 days/Ambient 7 days/Frozen 60 days

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)

Acceptable:

Specimen Type: Whole Blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 2 mL

Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Refrigerate (preferred) 7 days/Ambient 48 hours

• Informed Consent for Genetic Testing
• Biochemical Genetics Patient Information
• Blood Spot Collection Card-Spanish Instructions
• Blood Spot Collection Card-Chinese Instructions
• Informed Consent for Genetic Testing (Spanish)
• Blood Spot Collection Instructions

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602)

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Blood Spots: 1

Whole Blood: 0.5 mL

Supporting the biochemical diagnosis of mucopolysaccharidoses types II, IIIA, IIIB, IIIC, IVA, IVB, VI, and VII, and of multiple sulfatase deficiency

This test is not useful for carrier detection.

This test is a screening panel for individuals with clinical signs and symptoms suspicious for one of several mucopolysaccharidoses (MPS types II, IIIA, IIIB, IIIC, IVA, IVB, VI, or VII) or for multiple sulfatase deficiency. Enzymatic analysis for MPS IIID is not included in this assay, however it is included on MCL test MP9W. If an enzyme deficiency is detected by this screening test, additional biochemical or molecular testing is required to confirm a diagnosis.

Testing begins with screening for mucopolysaccharidoses. If results are normal or indicate mucopolysaccharidosis VII, testing is complete.

If results indicate mucopolysaccharidoses II, IIIA, IIIB, IIIC, IVA, IVB, or VI, quantitation of heparan sulfate, dermatan sulfate and keratan sulfate may be performed at an additional charge.

The mucopolysaccharidoses (MPS) are a group of disorders caused by a 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 lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG which affects multiple organ systems. These disorders have a broad clinical spectrum and can present with coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature, and skeletal abnormalities. This assay detects 8 of the 11 known MPS, including MPSII, MPSIIIA, MPSIIIB, MPSIIIC, MPSIVA, MPSIVB, MPSVI, and MPSVII.

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal disorder caused by mutations in the sulfatase-modifying factor 1 (SUMF1) gene. SUMF1 encodes for a formylglycine-generating enzyme that performs a critical posttranslational modification necessary for activation of all human sulfatases, including arylsulfatase A and B. The clinical features of MSD resemble symptoms of every single sulfatase deficiency, including metachromatic leukodystrophy, the mucopolysaccharidoses, X-linked ichthyosis, and chondrodysplasia punctata type I. Age of onset and clinical severity are variable and correspond with the level of residual enzyme activity. Individuals with MSD typically demonstrate reduced activity of several sulfatase enzymes including those on this panel (iduronate-2-sulfatase, heparan sulfate sulfatase, galactosamine-6-sulfate sulfatase, and arylsulfatase B).

Mucolipidosis II (MLII), also known as I-cell disease, is a rare autosomal recessive disorder with features of both mucopolysaccharidoses and sphingolipidoses. I-cell disease is a progressive disorder characterized by congenital or early infantile manifestations including coarse facial features, short stature, skeletal anomalies, cardio- and hepatomegaly, and developmental delays. While not intended for I-cell disease, a pattern of reduced activity of several enzymes and increased activity of others may indicate MLII.

Iduronate-2-sulfatase: >4.30 nmol/mL/hour

Heparan-N-sulfatase: >0.06 nmol/mL/hour

N-acetyl-alpha-D-glucosaminidase: >0.70 nmol/mL/hour

Heparan-alpha-glucosaminide N-acetyltransferase: >0.50 nmol/mL/hour

N-acetylgalactosamine-6-sulfatase: >0.70 nmol/mL/hour

Beta-galactosidase: >1.30 nmol/mL/hour

Arylsulfatase B: >0.90 nmol/mL/hour

Beta-glucuronidase: >2.60 nmol/mL/hour

An interpretive report will be provided.

Abnormal results are not sufficient to establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on this assay, additional biochemical or molecular genetic analyses are required.

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing, and in vitro, confirmatory studies (enzyme assay, molecular genetic analysis), and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

Beta-galactosidase is reduced in patients with galactosialidosis. Those patients will also demonstrate deficient activity of neuraminidase which is not evaluated on this panel. If there is clinical suspicion of galactosialidosis, order test OLIGU / Oligosaccharide Screen, Random, Urine.

Mucolipidosis II (MLII, I-cell disease) may not be detectable by this assay. If there is clinical suspicion of MLII, order test LSDS / Lysosomal Storage Disorders Screen, Random, Urine, NAGS / Hexosaminidase A and Total Hexosaminidase, Serum, and/or molecular genetic analysis of the GNPTAB gene, L test CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies, Gene List ID: IEMCP-L5VNMC)

The enzyme for MPSIIID (N-acetylglucosamine 6-sulfatase) is not evaluated on this panel.

Individuals with pseudodeficiency alleles can show reduced enzyme activity.

Carrier status (heterozygosity) for these conditions cannot be reliably detected.

Enzyme levels may be normal in individuals receiving enzyme replacement therapy or who have undergone hematopoietic stem cell transplant.

1. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. Eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; Accessed July 18, 2023. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225544161

2. Hopwood JJ, Ballabio A. Multiple sulfatase deficiency and the nature of the sulfatase family. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. Eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; Accessed July 18, 2023. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225546905

One dried blood spot sample (DBS) is incubated with a mix of substrate and internal standard (IS) for iduronate 2-sulfatase, heparan N-sulfatase, alpha-N-acetylglucosaminidase, N-acetylgalactosamine-sulfate, beta-galactosidase, arylsulfatase B, beta-glucuronidase, and tripeptidyl peptidase 1. A second DBS sample is incubated with a mix of substrate and IS for acetyl-CoA:alpha-glucosaminide N-acetyltransferase; and a third DBS sample with a mix of substrate and IS for palmitoyl-protein thioesterase 1. Following overnight incubation, the samples are combined, extracted by liquid-liquid extraction, and analyzed by 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.

82657

83864 (if appropriate)