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Test ID: ARSU Arylsulfatase A, 24 Hour, Urine

Reporting Name

Arylsulfatase A, U

Useful For

Detection of arylsulfatase A deficiency using urine specimens

 

This test is not suitable for carrier detection.

Specimen Type

Urine


Advisory Information


The preferred test to rule-out metachromatic leukodystrophy is ARSAW / Arylsulfatase A, Leukocytes.



Shipping Instructions


Specimen must be received at least 1 day prior to assay day for processing.



Necessary Information


24-Hour volume is required.



Specimen Required


Supplies: Urine Tubes, 10 mL (T068)

Container/Tube: Plastic, 10-mL tube

Specimen Volume: 6 mL

Collection Instructions:

1. Collect a 24-hour urine specimen.

2. No preservative.

3. Refrigerate specimen during collection.

Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens in Special Instructions for multiple collections.


Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated 14 days

Reference Values

≥19 nmol/h/mL

Note: Results from this assay may not reflect carrier status because of individual variation of arylsulfatase A enzyme levels.

Day(s) and Time(s) Performed

Friday

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

84311

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ARSU Arylsulfatase A, U 42726-0

 

Result ID Test Result Name Result LOINC Value
8777 Arylsulfatase A, U 42726-0
37423 Interpretation (ARSU) 59462-2
37413 Reviewed By 18771-6

Clinical Information

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of the arylsulfatase A (ARSA) enzyme, which leads to the accumulation of sulfatides (both galactosyl and lactosyl sulfatide) in the white matter of the central nervous system, the peripheral nervous system, and to a lesser extent, in visceral organs including the kidney and gallbladder. Cells that produce myelin are especially affected causing the characteristic leukodystrophy seen in MLD. Patients with MLD excrete excessive amounts of sulfatides in their urine.

 

The 3 clinical forms of MLD are late-infantile, juvenile, and adult, depending on age of onset. All forms result in progressive neurologic changes and leukodystrophy demonstrated on magnetic resonance imaging. Late-infantile MLD is the most common (50%-60% of cases) and usually presents before 30 months of age with hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration occurs and, unless successfully treated, most patients do not survive past childhood. Juvenile MLD (20%-30% of cases) is characterized by onset between 30 months to 16 years. Presenting features are behavior problems, declining school performance, clumsiness, and slurred speech. Neurodegeneration occurs at a somewhat slower and more variable rate than the late-infantile form. Adult MLD (15%-20% of cases) has an onset after puberty and can be as late as the fourth or fifth decade. Presenting features are often behavior and personality changes, including psychiatric symptoms. Clumsiness, neurologic symptoms, and seizures are also common. The disease course has variable progression and may occur over 2 to 3 decades. The disease prevalence is estimated to be approximately 1 in 100,000.

 

MLD is an autosomal recessive disorder and is caused by variants in the ARSA gene coding for the  ARSA enzyme. This disorder is distinct from conditions caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase deficiency). Saposin B deficiency is a rare autosomal recessive disorder with symptoms that mimic MLD; however, the ARSA enzyme level is normal. Like MLD, patients with saposin B deficiency can also excrete excessive amounts of sulfatides in their urine. Individuals with multiple sulfatase deficiency, which is clinically distinct from MLD, will also have deficiency of arylsulfatase A, however, other sulfatase enzymes will also be deficient.

 

Individuals with "pseudodeficiency" of ARSA have very low levels of ARSA activity, but are otherwise healthy. Pseudodeficiency is being recognized with increasing frequency among patients with other apparently unrelated neurologic conditions as well as among the general population, therefore a diagnosis of MLD cannot be based upon reduced ARSA activity alone  Additional studies, such as molecular genetic testing of ARSA (ARSAZ / ARSA Gene, Full Gene Analysis, Varies), urinary excretion of sulfatides (CTSA / Ceramide Trihexosides and Sulfatides, Urine), and/or histological analysis for metachromatic lipid deposits in nervous system tissue are recommended to confirm a diagnosis.

 

Current treatment options for MLD are focused on managing disease manifestations such as seizures, decline in mobility and cognitive ability, and feeding difficulties. Hematopoietic stem cell transplantation (HSCT) is an option but outcomes are dependent on the clinical stage and the presence of neurologic symptoms.

Interpretation

Reduced levels of arylsulfatase A are seen in patients with metachromatic leukodystrophy (MLD).

 

Individuals with pseudodeficiency of arylsulfatase A can have results in the affected range, but are otherwise unaffected with MLD.

 

Abnormal results should be confirmed using CTSA / Ceramide Trihexosides and Sulfatides, Urine. If molecular confirmation is desired, consider molecular genetic testing ARSAZ / ARSA Gene, Full Gene Analysis, Varies.

Clinical Reference

1. Gieselmann V, Ingeborg K:  Metachromatic Leukodystrophy. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al.  New York, NY: McGraw-Hill; 2014. Accessed 3/14/17. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546629&bookid=2709&jumpsectionid=225546643&Resultclick=2

2. Gomez-Ospina N: Arylsulfatase A Deficiency. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle. Updated 2017 Dec 14. Available at www.ncbi.nlm.nih.gov/books/NBK1130/

3. Mahmood A, Berry J, Wenger D, et al: Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review of the literature. J Child Neurol 2010;25(5):572-580

4. van Rappard DF, Boelens JJ, Wolf NI: Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. Best Pract Res Clin Endocrinol Metab 2015 Mar;29(2):261-273. doi: 10.1016/j.beem.2014.10.001

Analytic Time

9 days

Method Name

Colorimetric, Enzyme Assay

Urine Preservative Collection Options

Note: The addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection.

Ambient

No

Refrigerate

Required

Frozen

No

50% Acetic Acid

No

Boric Acid

No

Diazolidinyl Urea

No

6M Hydrochloric Acid

No

6M Nitric Acid

No

Sodium Carbonate

No

Thymol

No

Toluene

No

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

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

3. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical