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Test ID MPS3B Mucopolysaccharidosis III, Three-Enzyme Panel, Blood Spot


Necessary Information


1. Patient's age is required.

2. Reason for testing is required



Specimen 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 older than 1 year 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


Forms

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.

Useful For

Supporting the biochemical diagnosis of mucopolysaccharidoses types IIIA, IIIB, IIIC

 

This test is not useful for carrier detection.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MPSBS Mucopolysaccharidosis, BS Yes No

Testing Algorithm

If results are normal, testing is complete.

 

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

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

MPS III (Three) Panel, BS

Specimen Type

Whole blood

Specimen Minimum Volume

Blood spots: 1
Whole blood: 0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole blood Varies

Reject Due To

Blood spot specimen that shows serum rings or has multiple layers Reject
Insufficient specimen Reject
Unapproved filter papers Reject

Clinical Information

Mucopolysaccharidosis III (MPS III; Sanfilippo syndrome) is caused by reduced or absent activity of 1 of 4 enzymes involved in heparan sulfate degradation. Patients with MPS III uniformly excrete heparan sulfate resulting in similar clinical phenotypes and are further classified as type A, B, C, or D based upon the specific enzyme deficiency. MPS III is characterized by severe central nervous system (CNS) degeneration but only mild physical disease. Such disproportionate involvement of the CNS is unique among the MPS. Onset of clinical features, most commonly behavioral problems and delayed development, usually occurs between 2 and 6 years of age in a child who previously appeared normal. Severe neurologic degeneration occurs in most patients by 6 to 10 years of age accompanied by a rapid deterioration of social and adaptive skills with death generally occurring by their 20s. The occurrence of MPS III varies by subtype with types A and B being the most common and types C and D being very rare. The collective incidence is approximately 1 in 58,000 live births. This assay detects 3 of the 4 MPSIII types (MPS IIIA, IIIB, and IIIC).

 

A diagnostic workup for MPS typically also includes GAG determination in urine (MPSQU / Mucopolysaccharides Quantitative, Random, Urine) or blood (MPSBS / Mucopolysaccharidosis, Blood Spot or MPSER / Mucopolysaccharides Quantitative, Serum) and molecular genetic analysis of the relevant gene(s). For MPS III, a molecular panel is available that includes SGSH, NAGLU, GNS, HGSNAT (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify Gene List ID: IEMCP-7YM613).

Reference Values

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

 

An interpretive report will be provided.

Interpretation

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.

Cautions

The enzyme for mucopolysaccharidosis (MPS) IIID (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.

Clinical Reference

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 17, 2023. 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 17, 2023. https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225546905

Method Description

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)

Day(s) Performed

Thursday

Report Available

8 to 15 days

Test Classification

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.

CPT Code Information

82657

83864 (if appropriate)

NY State Approved

Yes