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Test ID: ARSAW Arylsulfatase A, Leukocytes

Reporting Name

Arylsulfatase A, Leukocytes

Useful For

Preferred test for detection of metachromatic leukodystrophy

Specimen Type

Whole Blood ACD


Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 96 hours of draw to be stabilized. Draw specimen Monday through Thursday only and not the day before a holiday. Specimen should be drawn and packaged as close to shipping time as possible.



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Do not transfer blood to other containers.


Specimen Minimum Volume

5 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood ACD Refrigerated (preferred) 4 days
  Ambient  4 days

Reference Values

≥62 nmol/h/mg

Note: Results from this assay may not reflect carrier status because of individual variation of arylsulfatase A enzyme levels. Low normal values may be due to the presence of pseudodeficiency gene or carrier gene. Patients with these depressed levels may be phenotypically normal.

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Assay is performed 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

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ARSAW Arylsulfatase A, Leukocytes In Process

 

Result ID Test Result Name Result LOINC Value
8779 Arylsulfatase A, Leukocytes 24078-8
32437 Interpretation 59462-2
32438 Reason for referral 42349-1
32439 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 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. Patients with MLD excrete excessive amounts of sulfatides in their urine.

 

The 3 clinical forms of MLD are late-infantile, juvenile, and adult, which are categorized based 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 between 6 months to 2 years of age with hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration occurs with most patients dying 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 fairly common polymorphisms 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 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

Decreased enzyme levels indicate an individual is affected with metachromatic leukodystrophy (MLD). Note that individuals with pseudodeficiency of arylsulfatase A can have results in this 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.

Clinical Reference

1. Gieselmann V, Ingeborg KGieselmann V, e:  Metachromatic Leukodystrophy. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, 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. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. 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

8 days

Method Name

Colorimetric Enzyme Assay

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:

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