Test Catalog

Test Id : MPSQU

Mucopolysaccharides Quantitative, Random, Urine

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

Supporting the biochemical diagnosis of one of the mucopolysaccharidoses: types I, II, III, IV, VI, or VII

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

This test is used to aid in the diagnosis and monitoring of patients with mucopolysacchariodoses (MPS) types I, II, III, IV, VI, and VII.

 

Accumulation of undegraded glycosaminoglycans (GAG) leads to progressive cellular dysfunction and results in the typical clinical features seen with this group of disorders.

 

Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS) and chondroitin-6-sulfate (C6S) are markers for a subset of MPS.

 

DS and HS in urine are markers for MPS types I, II, III, VI and VII.

 

KS in urine is a marker for MPS IVA and MPS IVB.

 

C6S in urine is a marker for MPS IVA and MPS VII.

Highlights

Using liquid chromatography-tandem mass spectrometry, this quantitative urine mucopolysaccharide screen provides analysis of the specific sulfates that are associated with at least 13 different disorders.

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

For more information see Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 in Special Instructions

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

Method Name
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Mucopolysaccharides Quant, U

Aliases
Lists additional common names for a test, as an aid in searching

Arylsulfatase B Deficiency

Beta-Galactosidase Deficiency

Beta-Glucuronidase Deficiency

Chondroitin-6-sulfate

Chondroitin-6 sulfate

Dermatan Sulfate

GAGS (Glycosaminoglycans)

Galactose-6-Sulfatase Deficiency

Glycosaminoglycans (GAGS)

Heparan Sulfate

Hunter syndrome

Hurler syndrome

Hurler-Scheie syndrome

Iduronate Sulfatase Deficiency

Iduronidase Deficiency

Keratan Sulfate

Maroteaux Lamy syndrome

Maroteaux-Lamy syndrome

Morquio A

Morquio B

Mucopolysaccharides

Mucopolysaccharidosis I (MPS I)

Mucopolysaccharidosis II (MPS II)

Mucopolysaccharidosis III (MPS III)

Mucopolysaccharidosis IV (MPS IVA)

Mucopolysaccharidosis IV (MPS IVB)

Mucopolysaccharidosis VI (MPS VI)

Mucopolysaccharidosis VII (MPS VII)

Multiple sulfatase deficiency

Sanfilippo syndrome

Scheie syndrome

Sly syndrome

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

For more information see Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 in Special Instructions

Specimen Type
Describes the specimen type validated for testing

Urine

Ordering Guidance

This test alone is not appropriate for the diagnosis of a specific mucopolysaccharidosis (MPS). Follow-up enzymatic or molecular genetic testing must be performed to confirm a diagnosis of an MPS.

Necessary Information

1. Patient's age is required.

2. Reason for testing is required.

3. Biochemical Genetics Patient Information (T602) in Special Instructions is recommended. This information aids in providing a more thorough interpretation of results. Send information with specimen.

4. If not ordering electronically, Biochemical Genetics Patient Information (T602, in Special Instructions) is required. Send information with specimen.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
BG716 Reason for Referral Rule out Mucopolysaccharidoses
Follow up of abnormal newborn screening
Known patient on treatment
Known GM1 patient
Known MPS I patient
Known MPS II patient
Known MPS III patient
Known MPS IVA patient
Known MPS IVB patient
Known MPS VI patient
Known MPS VII patient
Known MSD patient
Known Fucosidosis patient
Not Provided

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Do not administer low-molecular weight heparin prior to collection

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Container/Tube: Plastic, 5-mL urine tube

Specimen Volume: 2 mL

Pediatric Volume: 1 mL

Collection Instructions: Collect a random urine specimen (early morning preferred).

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

Forms

1.  Biochemical Genetics Patient Information (T602) in Special Instructions

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 90 days
Frozen 365 days
Ambient 7 days

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

Supporting the biochemical diagnosis of one of the mucopolysaccharidoses: types I, II, III, IV, VI, or VII

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

This test is used to aid in the diagnosis and monitoring of patients with mucopolysacchariodoses (MPS) types I, II, III, IV, VI, and VII.

 

Accumulation of undegraded glycosaminoglycans (GAG) leads to progressive cellular dysfunction and results in the typical clinical features seen with this group of disorders.

 

Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS) and chondroitin-6-sulfate (C6S) are markers for a subset of MPS.

 

DS and HS in urine are markers for MPS types I, II, III, VI and VII.

 

KS in urine is a marker for MPS IVA and MPS IVB.

 

C6S in urine is a marker for MPS IVA and MPS VII.

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

For more information see Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 in Special Instructions

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-6-sulfate, which are collectively called glycosaminoglycans (GAG). Undegraded or partially degraded GAG are stored in lysosomes and excreted in the urine. Accumulation of GAG in lysosomes interferes with normal functioning of cells, tissues, and organs resulting in the clinical features observed in mucopolysaccharidosis (MPS) disorders. There are 11 known enzyme deficiencies that result in the accumulation of GAG. In addition, abnormal GAG storage is observed in multiple sulfatase deficiency and in I-cell disease. Finally, abnormal excretion of GAG in urine is observed occasionally in other disorders including active bone diseases, connective tissue disease, hypothyroidism, urinary dysfunction, and oligosaccharidoses.

 

Mucopolysaccharidoses are autosomal recessive disorders except for MPS II, which follows an X-linked inheritance pattern. Affected individuals typically experience a period of normal growth and development followed by progressive disease involvement encompassing multiple systems. The severity and features vary and may include facial coarsening, organomegaly, skeletal changes, cardiac abnormalities, and developmental delays. Moreover, disease presentation varies from as early as late infancy to adulthood.

 

A diagnostic workup for individuals with suspected MPS should begin with this test, which includes the quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the specific sulfates or GAG. Interpretation is based upon pattern recognition of the specific sulfates detected by MS/MS and the quantitative analysis of their amounts of excretion. However, an abnormal mucopolysaccharide analysis is not sufficient to conclusively establish a specific diagnosis. It is strongly recommended to seek confirmation by an independent method, typically in vitro enzyme assay (available in either blood or cultured fibroblasts from a skin biopsy) or molecular analysis.

 

After a specific diagnosis has been established, this test can be appropriate for monitoring the effectiveness of treatment, such as a bone marrow transplant or enzyme replacement therapy. This test allows for monitoring of the excretion of specific sulfates, as these may change in patients with an MPS disorder undergoing treatment.

 

Table: Enzyme Defects and Excretion Products of Mucopolysaccharidoses

Disorder

Alias

Enzyme deficiency

 

Sulfates excreted

MPS I

Hurler/Scheie

Alpha-L-iduronidase

DS/HS

MPS II

Hunter

Iduronate 2-sulfatase

DS/HS

MPS III A

Sanfilippo A

Heparan N-sulfatase

HS

MPS III B

Sanfilippo B

N-acetyl-alpha-D-glucosaminidase

HS

MPS III C

Sanfilippo C

Acetyl-CoA:alpha-glucosaminide N-acetyltransferase

HS

MPS III D

Sanfilippo D

N-acetylglucosamine-6-sulfatase

HS

MPS IV A

Morquio A

Galactosamine-6-sulfatase

KS/C6S

MPS IV B

Morquio B

Beta-galactosidase

KS

MPS VI

Maroteaux-Lamy

Arylsulfatase B

DS

MPS VII

Sly

Beta-glucuronidase

DS, HS, C6S

MPS IX

Hyaluronidase deficiency

Hyaluronidase

None

KEY: C6S, chondroitin 6-sulfate; DS, dermatan sulfate; HS, heparan sulfate; KS, keratan sulfate

 

MPS I (Hurler/Scheie syndrome) is caused by a reduced or absent activity of the alpha-L-iduronidase enzyme. The incidence of MPS I is approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy. This enzyme deficiency results in a wide range of clinical phenotypes that are further categorized into 3 main types: MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS IH/S (Hurler-Scheie syndrome), which are not typically distinguishable via biochemical methods. Clinically, they are also referred to as MPS I and attenuated MPS I. MPS IH is the most severe and has an early onset consisting of skeletal deformities, coarse facial features, hepatosplenomegaly, macrocephaly, cardiomyopathy, hearing loss, macroglossia, and respiratory tract infections. Developmental delay is noticed as early as 12 months of age, with death occurring usually before 10 years of age when left untreated. MPS IH/S has an intermediate clinical presentation characterized by progressive skeletal symptoms called dysostosis multiplex. Individuals typically have little or no intellectual dysfunction. Corneal clouding, joint stiffness, deafness, and valvular heart disease can develop by early to mid-teens. Survival into adulthood is common. Cause of death usually results from cardiac complications or upper airway obstruction. Comparatively, MPS IS presents with the mildest phenotype. The onset occurs after 5 years of age. It is characterized by normal intelligence and stature; however, affected individuals do experience joint involvement, visual impairment, and obstructive airway disease.

 

MPS II (Hunter syndrome) is caused by a reduced or absent activity of the enzyme iduronate 2-sulfatase. The clinical features and severity of symptoms of MPS II are widely variable ranging from severe disease to an attenuated form, which generally presents at a later onset with a milder clinical presentation. In general, 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. The clinical presentation of MPS II is similar to that of MPS I with the notable difference of the lack of corneal clouding in MPS II. The inheritance pattern is X-linked and as such MPS II is observed almost exclusively in male patients with an estimated incidence of 1 in 170,000 male births. Female patients who are symptomatic carriers are very rare but have been reported.  Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

 

MPS III (Sanfilippo syndrome) is caused by a reduced or absent activity of 1 of 4 enzymes (see Table above), resulting in a defect of 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 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. Death generally occurs by the third decade of life (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. Treatment options are limited to symptomatic management.

 

MPS IVA (Morquio A syndrome) is caused by a reduced or absent N-acetylgalactosamine-6-sulfate sulfatase. Clinical features and severity of symptoms of MPS IVA are widely variable but may include skeletal dysplasia, short stature, dental anomalies, corneal clouding, respiratory insufficiency, and cardiac disease. Intelligence is usually normal. Estimates of the incidence of MPS IVA syndrome range from 1 in 200,000 to 1 in 300,000 live births. Treatment with enzyme replacement therapy is available.

 

MPS IVB (Morquio B syndrome) is caused by a reduced or absent beta-galactosidase activity, which gives rise to the physical manifestations of the disease. Clinical features and severity of symptoms of MPS IVB are widely variable ranging from severe disease to an attenuated form, which generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, but no neurological involvement. The incidence of MPS IVB is estimated to be about 1 in 250,000 live births. Treatment options are limited to symptomatic management.

 

MPS VI (Maroteaux-Lamy syndrome) is caused by a deficiency of the enzyme arylsulfatase B. Clinical features and severity of symptoms are widely variable but typically include short stature, dysostosis multiplex, facial dysmorphism, stiff joints, claw-hand deformities, carpal tunnel syndrome, hepatosplenomegaly, corneal clouding, and cardiac defects. Intelligence is usually normal. Estimates of the incidence of MPS VI range from 1 in 200,000 to 1 in 300,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

 

MPS VII (Sly syndrome) is caused by a deficiency of the enzyme beta-glucuronidase. The phenotype varies significantly from mild to severe presentations and may include macrocephaly, short stature, dysostosis multiplex, hepatomegaly, coarse facies, and impairment of cognitive function. Likewise, the age of onset is variable ranging from prenatal to adulthood. MPS VII is extremely rare, affecting approximately 1 in 1,500,000 individuals. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

 

MPS IX is a very rare disorder caused by a deficiency of the enzyme hyaluronidase. Patients present with short stature, flat nasal bridge, and joint findings. Urine GAG are normal in MPS IX.

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.

DERMATAN SULFATE

< or =1.00 mg/mmol creatinine

 

HEPARAN SULFATE

< or =4 years: < or =0.50 mg/mmol creatinine

> or =5 years: < or =0.25 mg/mmol creatinine

 

CHONDROITIN-6 SULFATE

< or =24 months: < or =10.00 mg/mmol creatinine

25 months-10 years: < or =2.50 mg/mmol creatinine

> or =11 years: < or =1.50 mg/mmol creatinine

 

KERATAN SULFATE

< or =12 months: < or =2.00 mg/mmol creatinine

13-24 months: < or =1.50 mg/mmol creatinine

25 months-4 years: < or =1.00 mg/mmol creatinine

5-18 years: < or =0.50 mg/mmol creatinine

> or =19 years: < or =0.30 mg/mmol creatinine

Interpretation
Provides information to assist in interpretation of the test results

Elevations of dermatan sulfate and/or heparan sulfate and/or keratan sulfate and/or chondroitin-6-sulfate may be indicative of one of the mucopolysaccharidoses: types I, II, III, IV, VI, or VII.

 

Elevations of any or all sulfate species may be indicative of multiple sulfatase deficiency or mucolipidosis II/III.

 

Rarely, an elevation of keratan sulfate may be indicative of alpha-fucosidosis.

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

No significant cautionary statements

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

1. de Ru MH, van der Tol L, van Vlies N, et al: Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans. J Inherit Metab Dis. 2013 Mar;36(2):247-255

2. 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; 2019. Accessed August 03, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225544161

3. Puckett Y, Mallorga-Hernandez A, Montano AM: Epidemiology of mucopolysaccharidoses (MPS) in the United States: challenges and opportunities. Orphanet J Rare Dis. 2021 May 29;16(1):241

4. Freeze HH: Genetic disorders of glycan degradation. In: Varki A, Cummings RD, Esko JD, et al, eds. Essentials of Glycobiology. 2nd ed. Cold Spring Harbor Laboratory Press; 2009. Accessed August 12, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1934/

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

Method Description
Describes how the test is performed and provides a method-specific reference

Dermatan sulfate (DS), heparin sulfate (HS), keratan sulfate (KS) and chondroitin-6-sulfate (C6S) are enzymatically digested from urine. The reaction mixture is centrifuged and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The ratio of the extracted peak area of DS, HS, KS and C6S to internal standard as determined by LC-MS/MS is used to calculate the concentration of DS, HS, KS and C6S in the sample.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 15 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83864

82570

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
MPSQU Mucopolysaccharides Quant, U 94691-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
BG716 Reason for Referral 42349-1
605986 Dermatan Sulfate 94692-1
605987 Heparan Sulfate 94693-9
605988 Chondroitin-6 Sulfate 94690-5
605989 Keratan Sulfate 92806-9
605990 Interpretation 59462-2
605985 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports