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Test Code MPSQU Mucopolysaccharides Quantitative, Random, 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) is recommended. This information aids in providing a more thorough interpretation of results. Send information with specimen.



Specimen Required


Patient Preparation: For 6 hours before specimen collection, patient should not receive heparin.

Supplies: Sarstedt Aliquot Tube, 5 mL (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).


Forms

1. Biochemical Genetics Patient Information (T602)

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

Useful For

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

Testing Algorithm

For more information see the following:

-Lysosomal Disorders Diagnostic Algorithm, Part 1

-Newborn Screening Follow up for Mucopolysaccharidosis type II

 

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

Method Name

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

Reporting Name

Mucopolysaccharides Quant, U

Specimen Type

Urine

Specimen Minimum Volume

1 mL

Specimen Stability Information

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

Reject Due To

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

Clinical Information

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 (ERT). 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

 

Mucopolysaccharidosis I is caused by a reduced or absent activity of the alpha-L-iduronidase enzyme due to disease-causing variant in the IDUA gene. MPS I can result in a wide range of phenotypes categorized into 3 syndromes: Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S). Because these syndromes cannot be distinguished biochemically, they are also referred to as MPS I and attenuated MPS I. Clinical features and severity of symptoms of MPS I are variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, intellectual disabilities or learning difficulties, and cardiac valvular disease. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy (ERT).

 

Mucopolysaccharidosis II (Hunter syndrome) is caused by a reduced or absent activity of the enzyme iduronate 2-sulfatase due to disease-causing variants in the IDS gene. 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 in 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, although symptomatic females have been reported. Treatment options include hematopoietic stem cell transplantation and ERT.

 

Mucopolysaccharidosis 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, 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. Treatment options are limited to symptomatic management.

 

Mucopolysaccharidosis IVA (Morquio A syndrome) is caused by a reduced or absent N-acetylgalactosamine-6-sulfate sulfatase due to disease-causing variants in the GALNS gene. Clinical features and severity of symptoms of MPS IVA are variable and may include skeletal dysplasia, short stature, dental anomalies, corneal clouding, respiratory insufficiency, cardiac disease, and no neurologic involvement. Treatment with ERT is available.

 

Mucopolysaccharidosis IVB (Morquio B syndrome) is caused by a reduced or absent beta-galactosidase activity due to disease-causing variants in the GLB1 gene. Clinical features and severity of symptoms of MPS IVB are 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. Treatment options are limited to symptomatic management.

 

Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is caused by a deficiency of the enzyme arylsulfatase B due to disease-causing variants in the ARSB gene. Clinical features and severity of symptoms are variable and typically include short stature, dysostosis multiplex, facial dysmorphism, stiff joints, claw-hand deformities, carpal tunnel syndrome, hepatosplenomegaly, corneal clouding, cardiac defects, and no neurological involvement. Treatment options include hematopoietic stem cell transplantation and ERT.

 

Mucopolysaccharidosis VII (Sly syndrome) is caused by a deficiency of the enzyme beta-glucuronidase due to disease-causing variants in the GUSB gene. 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. Treatment options include hematopoietic stem cell transplantation and ERT.

 

Mucopolysaccharidosis IX is a very rare disorder caused by a deficiency of the enzyme hyaluronidase due to disease-causing variants in the HYAL1 gene. Patients present with short stature, flat nasal bridge, and joint findings. Urine GAG are normal in MPS IX.

Reference Values

Dermatan Sulfate

≤1.00 mg/mmol creatinine

 

Heparan Sulfate

≤4 years: ≤0.50 mg/mmol creatinine

≥5 years: ≤0.25 mg/mmol creatinine

 

Chondroitin-6 Sulfate

≤24 months: ≤10.00 mg/mmol creatinine

25 months-10 years: ≤2.50 mg/mmol creatinine

≥11 years: ≤1.50 mg/mmol creatinine

 

Keratan Sulfate

≤12 months: ≤2.00 mg/mmol creatinine

13-24 months: ≤1.50 mg/mmol creatinine

25 months-4 years: ≤1.00 mg/mmol creatinine

5-18 years: ≤0.50 mg/mmol creatinine

≥19 years: ≤0.30 mg/mmol creatinine

Interpretation

Elevations of dermatan sulfate, heparan sulfate, 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

Administration of heparin before specimen collection may interfere with this assay and results should be interpreted with caution.

Day(s) Performed

Monday

Report Available

4 to 10 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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

83864

82570

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MPSQU Mucopolysaccharides Quant, U 94691-3

 

Result ID Test Result Name Result LOINC Value
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