Sign in →

Test ID: ARSU Arylsulfatase A, 24 Hour, Urine

Reporting Name

Arylsulfatase A, U

Useful For

Detection of metachromatic leukodystrophy in urine specimens

Specimen Type

Urine


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 (T068)

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 in Special Instructions for multiple collections.


Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time
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

Specimens are processed on Monday. Assay is performed on Tuesday; 8 a.m.

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 In Process

 

Result ID Test Result Name Result LOINC Value
8777 Arylsulfatase A, U 42726-0
37423 Interpretation (ARSU) 59462-2
37413 Reviewed By No LOINC Needed

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 galactosyl sulfatide (cerebroside sulfate) in the white matter of the central nervous system and in the peripheral nervous system. Galactosyl sulfatide and, to a smaller extent, lactosyl sulfatide, also accumulate within the kidney, gallbladder, and other visceral organs and are excreted in excessive amounts in the urine.

 

The 3 clinical forms of MLD are late-infantile, juvenile, and adult, depending on age of onset. All 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 between age 1 to 2 years with hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration occurs and most patients die within 5 years of the diagnosis. Juvenile MLD (20%-30% of cases) is characterized by onset between 4 to 14 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 mutations 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 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.

 

Extremely low ARSA levels have been found in some clinically normal parents and other relatives of MLD patients. These individuals do not have metachromatic deposits in peripheral nerve tissues, and their urine content of sulfatide is normal. Individuals with this "pseudodeficiency" have been recognized with increasing frequency among patients with other apparently unrelated neurologic conditions as well as among the general population. This has been associated with a fairly common polymorphism in the ARSA gene which leads to low expression of the enzyme (5%-20% of normal). These patients can be difficult to differentiate from actual MLD patients. Additional studies, such as molecular genetic testing of ARSA (ARSAZ / ARSA Gene, Full Gene Analysis), 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. Bone marrow transplantation remains controversial, and the effectiveness of enzyme replacement therapy may be limited due to difficulties crossing the blood-brain barrier. Other treatments under ongoing investigation include hematopoietic stem cell transplantation and fetal umbilical cord blood transplantation.

Interpretation

Greatly reduced levels of arylsulfatase A in urine (≤15 nmol/h/mL), as well as in serum and various tissues, is seen in patients with metachromatic leukodystrophy.

 

Individuals with pseudoarylsulfatase A deficiency can have results in the affected range, but are otherwise unaffected with metachromatic leukodystrophy.

 

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.

Clinical Reference

1. Gieselmann V, Ingeborg K. Gieselmann V, et al: 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 March 14, 2017. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62644361

2. Fluharty AL: Arylsulfatase A Deficiency. 2006 May 30 In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Seattle, WA: University of Washington, Seattle. Updated 2014 Feb 6. 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

Ambient

No

Refrigerated

Required

Frozen

No

6N HCl

No

50% Acetic Acid

No

Na2CO3

No

Toluene

No

6N HNO3

No

Boric Acid

No

Thymol

No

 

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical