Arylsulfatase A, Leukocytes
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Detection of metachromatic leukodystrophy
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Preferred test to rule out metachromatic leukodystrophy. Not reliable in identifying carriers due both to analytical variation and unusual genetic variants.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Colorimetric Enzyme Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Arylsulfatase A, Leukocytes
ARYLSULFATASE A (WBC)
Arylsulfatase A Deficiency
WBC Aryl Sulfatase A
ARYLSULFATASE A (WBC)
Arylsulfatase A Deficiency
WBC Aryl Sulfatase A
Specimen Type Describes the specimen type needed for testing
Whole Blood ACD
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive 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.
Preferred: Yellow top (ACD solution B)
Acceptable: Yellow top (ACD solution A)
Specimen Volume: 7 mL
Collection Instructions: Do not transfer blood to other containers.
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 (Supply T576) is available in Special Instructions.
2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Specimen >96 hours old
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood ACD||Refrigerated (preferred)||4 days|
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 enzyme. MLD follows an autosomal recessive inheritance pattern and is caused by mutations in the ARSA gene. Deficiency of the arylsulfatase A enzyme 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 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 typically 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 is characterized by onset between 4 to 14 years. Typical 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 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.
Extremely low arylsulfatase A levels have been found in some clinically normal parents and other relatives of MLD patients. These individuals do not have metachromatic deposits, 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 (ARSAS/61259 ARSA Gene, Full Gene Analysis), urinary excretion of sulfatides (CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, 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 usually 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.
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 or carrier gene. Patients with these depressed levels may be phenotypically normal.
Decreased enzyme levels indicate an individual is affected with metachromatic leukodystrophy (MLD). Note that individuals with pseudoarylsulfatase A deficiency can have results in this range, but are otherwise unaffected with MLD.
Abnormal results should be confirmed using CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine. If molecular confirmation is desired, consider molecular genetic testing ARSAS/61259 ARSA Gene, Full Gene Analysis.
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.
Individuals with pseudodeficiency of arylsulfatase A may have decreased enzyme activity and are not clinically affected with MLD.
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 Provides recommendations for further in-depth reading of a clinical nature
1. Jaeken J, Gieselmann V, von Figura K: Metachromatic leukodystrophy. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, available at www.ommbid.com. Accessed 03/05/2013
2. Fluharty AL: Arylsulfatase A Deficiency. Available from URL: http://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. Journal of Child Neurology 2009; 25(5):572-580.
Method Description Describes how the test is performed and provides a method-specific reference
p-Nitrocatechol sulfate (2-hydroxy-5-nitrophenyl sulfate) is used as an analog to the natural substrate. The reaction yields p-nitrocatechol, which is measured at 515 nm.(Shapira E, Blitzer MG, Africk DK, Miller JB: Enzyme Assays: Arylsulfatase A Activity, Biochemical Genetics. A Laboratory Manual 1989, pp 41-42)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Specimens are processed Monday through Sunday.
Assay is performed Thursday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
WBC homogenate stored 1 month
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|8779||Arylsulfatase A, Leukocytes||24078-8|
|32438||Reason for referral||42349-1|