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Test Catalog

Test ID: ARSAW    
Arylsulfatase A, Leukocytes

Useful For Suggests clinical disorders or settings where the test may be helpful

Preferred enzymatic test for detection of arylsulfatase A deficiency

 

This test is not suitable for carrier detection.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is the preferred test to rule-out metachromatic leukodystrophy.

 

Metachromatic leukodystrophy (MLD) is caused by deficient activity of arylsulfatase A (ARSA) enzyme and is characterized by progressive neurologic changes and leukodystrophy with variable age of onset.

 

Pseudodeficiency of arylsulfatase A (ARSA) enzyme has been recognized with increasing frequency among patients with other apparently unrelated neurologic conditions as well as among the general population.

 

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.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

> or =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 variant or carrier gene variant. Patients with these depressed levels may be phenotypically normal.

Interpretation Provides information to assist in interpretation of the test results

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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not reliable in identifying carriers due both to analytical variation and unusual genetic variants.

 

Arylsulfatase A is also deficient in individuals with multiple sulfatase deficiency.

 

This disorder is distinct from conditions caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase deficiency).

Clinical Reference Recommendations for in-depth reading of a clinical nature

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

Special Instructions Library of PDFs including pertinent information and forms related to the test