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Test ID MPSQU Mucopolysaccharides Quantitative, Random, Urine


Advisory Information


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



Necessary Information


1. Patient's age is required.

2. Reason for referral 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.



Specimen Required


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

Supplies: Aliquot Tube, 5 mL (T465)

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

If not ordering electronically, Biochemical Genetics Patient Information (T602, in Special Instructions) is required.

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 Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 in Special Instructions

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 Special Container
Urine Refrigerated (preferred) 90 days
  Frozen  365 days
  Ambient  7 days

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 (GAGs). Undegraded or partially degraded GAGs are stored in lysosomes and excreted in the urine. Accumulation of GAGs 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 mucopolysaccharides. In addition, abnormal glycosaminoglycan storage is observed in multiple sulfatase deficiency and in I-cell disease. Finally, abnormal excretion of GAGs 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 with the exception of 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 GAGs. 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) and/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 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, with death occurring usually before 10 years of age. 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 males with an estimated incidence of 1 in 170,000 male births. Symptomatic carrier females have been reported, but are very rare. 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. Sanfilippo syndrome 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.

 

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.

 

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

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 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 mucolipidosisII/III.

 

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

Clinical Reference

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;36:247-255

2. Neufeld EF, Muenzer J: The Mucopolysaccharidoses. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, S Antonarakis, A Ballabio, et al. McGraw-Hill. Accessed October 14, 2019.Available at http://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225544161

Day(s) and Time(s) Performed

Varies

Analytic Time

8 days

Test Classification

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 U.S. 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